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Journal of Gastroenterology
Published in: Journal of Gastroenterology 7/2013

01-07-2013 | Review

Cancer stem cells: the ‘heartbeat’ of gastric cancer

Authors: Guihua Xu, Jie Shen, Xiaohui Ou Yang, Masakiyo Sasahara, Xiulan Su

Published in: Journal of Gastroenterology | Issue 7/2013

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Abstract

Gastric cancer (GC) remains one of the most common cancers worldwide. Its prevalence is still on the rise in the developing countries due to the ageing population. The cancer stem cell (CSC) theory provides a new insight into the interpretation of tumor initiation, aggressive growth, recurrence, and metastasis of cancer, as well as the development of new strategies for cancer treatment. This review will focus on the progress of biomarkers and signaling pathways of CSCs, the complex crosstalk networks between the microenvironment and CSCs, and the development of therapeutic approaches against CSCs, predominantly focusing on GC.
Literature
1.
Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108.PubMedCrossRef
2.
Gill S, Shah A, Le N, Cook EF, Yoshida EM. Asian ethnicity-related differences in gastric cancer presentation and outcome among patients treated at a Canadian cancer center. J Clin Oncol. 2003;21:2070–6.PubMedCrossRef
3.
Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature. 2001;414:105–11.PubMedCrossRef
4.
5.
Furth J, Kahn M. The transmission of leukaemia of mice with a single cell. Am J Cancer. 1937;31:276–82.
6.
Bonnet D, Dick JE. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med. 1997;3:730–7.PubMedCrossRef
7.
Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA. 2003;100:3983–8.PubMedCrossRef
8.
Singh SK, Clarke ID, Terasaki M, Bonn VE, Hawkins C, Squire J, et al. Identification of a cancer stem cell in human brain tumors. Cancer Res. 2003;63:5821–8.PubMed
9.
Collins AT, Berry PA, Hyde C, Stower MJ, Maitland NJ. Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res. 2005;65:10946–51.PubMedCrossRef
10.
Fang D, Nguyen TK, Leishear K, Finko R, Kulp AN, Hotz S, et al. A tumorigenic subpopulation with stem cell properties in melanomas. Cancer Res. 2005;65:9328–37.PubMedCrossRef
11.
Yang ZF, Ngai P, Ho DW, Yu WC, Ng MN, Lau CK, et al. Identification of local and circulating cancer stem cells in human liver cancer. Hepatology. 2008;47:919–28.PubMedCrossRef
12.
Li C, Heidt DG, Dalerba P, Burant CF, Zhang L, Adsay V, et al. Identification of pancreatic cancer stem cells. Cancer Res. 2007;67:1030–7.PubMedCrossRef
13.
Hermann PC, Huber SL, Herrler T, Aicher A, Ellwart JW, Guba M, et al. Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell. 2007;1:313–23.PubMedCrossRef
14.
O’Brien CA, Pollett A, Gallinger S, Dick JE. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature. 2007;445:106–10.PubMedCrossRef
15.
Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C, et al. Identification and expansion of human colon-cancer-initiating cells. Nature. 2007;445:111–5.PubMedCrossRef
16.
Dalerba P, Dylla SJ, Park IK, Liu R, Wang X, Cho RW, et al. Phenotypic characterization of human colorectal cancer stem cells. Proc Natl Acad Sci USA. 2007;104:10158–63.PubMedCrossRef
17.
Prince ME, Sivanandan R, Kaczorowski A, Wolf GT, Kaplan MJ, Dalerba P, et al. Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. Proc Natl Acad Sci USA. 2007;104:973–8.PubMedCrossRef
18.
Clarke MF, Dick JE, Dirks PB, Eaves CJ, Jamieson CH, Jones DL, et al. Cancer stem cells-perspectives on current status and future directions: AACR workshop on cancer stem cells. Cancer Res. 2006;66:9339–44.PubMedCrossRef
19.
Brabletz S, Schmalhofer O, Brabletz T. Gastrointestinal stem cells in development and cancer. J Pathol. 2009;217:307–17.PubMedCrossRef
20.
Qiao XT, Gumucio DL. Current molecular markers for gastric progenitor cells and gastric cancer stem cells. J Gastroenterol. 2011;46:855–65.PubMedCrossRef
21.
Dewi DL, Ishii H, Kano Y, Nishikawa S, Haraguchi N, Sakai D, et al. Cancer stem cell theory in gastrointestinal malignancies: recent progress and upcoming challenges. J Gastroenterol. 2011;46:1145–57.PubMedCrossRef
22.
Xu G, Su XL, Shen J, Bi LF, Ou Yang XH. Regulation of ACBP on cell cycle of human stomach cancer cell BGC-823. Chin J Cancer Prev Treat. 2007;14:1361–4.
23.
Su XL, Ou Yang XH, Xu GH, Shen J, Wang ZY. Effect of ACBP-S on cell cycle and apoptosis in human gastric cancer cells. Zhonghua Zhong Liu Za Zhi. 2008;30:422–7.PubMed
24.
Su L, Xu G, Shen J, Tuo Y, Zhang X, Jia S, et al. Anticancer bioactive peptide suppresses human gastric cancer growth through modulation of apoptosis and the cell cycle. Oncol Rep. 2010;23:3–9.PubMed
25.
Rahman M, Deleyrolle L, Vedam-Mai V, Azari H, Abd-El-Barr M, Reynolds BA. The cancer stem cell hypothesis: failures and pitfalls. Neurosurgery. 2011;68:531–45.PubMedCrossRef
26.
Lee ER. Dynamic histology of the antral epithelium in the mouse stomach: I. Architecture of antral units. Am J Anat. 1985;172:187–204.PubMedCrossRef
27.
Lee ER, Leblond CP. Dynamic histology of the antral epithelium in the mouse stomach: II. Ultra-structure and renewal of isthmal cells. Am J Anat. 1985;172:205–24.PubMedCrossRef
28.
Lee ER. Dynamic histology of the antral epithelium in the mouse stomach: III. Ultrastructure and renewal of pit cells. Am J Anat. 1985;172:225–40.PubMedCrossRef
29.
Lee ER, Leblond CP. Dynamic histology of the antral epithelium in the mouse stomach: IV. Ultra-structure and renewal of gland cells. Am J Anat. 1985;172:241–59.PubMedCrossRef
30.
Saikawa Y, Fukuda K, Takahashi T, Nakamura R, Takeuchi H, Kitagawa Y. Gastric carcinogenesis and the cancer stem cell hypothesis. Gastric Cancer. 2010;13:11–24.PubMedCrossRef
31.
Bjerknes M, Cheng H. Multipotential stem cells in adult mouse gastric epithelium. Am J Physiol Gastrointest Liver Physiol. 2002;283:G767–77.PubMed
32.
Qiao XT, Ziel JW, McKimpson W, Madison BB, Todisco A, Merchant JL, et al. Prospective identification of a multi-lineage progenitor in murine stomach epithelium. Gastroenterology. 2007;133:1989–98.PubMedCrossRef
33.
Barker N, Huch M, Kujala P, van de Wetering M, Snippert HJ, van Es JH, et al. Lgr5(+ve) stem cells drive self-renewal in the stomach and build long-lived gastric units in vitro. Cell Stem Cell. 2010;6:25–36.PubMedCrossRef
34.
Scoville DH, Sato T, He XC, Li L. Current view: intestinal stem cells and signaling. Gastroenterology. 2008;134:849–64.PubMedCrossRef
35.
36.
Okamoto R, Yajima T, Yamazaki M, Kanai T, Mukai M, Okamoto S, et al. Damaged epithelia regenerated by bone marrow-derived cells in the human gastrointestinal tract. Nat Med. 2002;8:1011–7.PubMedCrossRef
37.
Avital I, Moreira AL, Klimstra DS, Leversha M, Papadopoulos EB, Brennan M, et al. Donor derived human bone marrow cells contribute to solid organ cancers developing after bone marrow transplantation. Stem Cells. 2007;25:2903–9.PubMedCrossRef
38.
Houghton J, Stoicov C, Nomura S, Rogers AB, Carlson J, Li H, et al. Gastric cancer originating from bone marrow-derived cells. Science. 2004;306:1568–71.PubMedCrossRef
39.
Okumura T, Wang SS, Takaishi S, Tu SP, Ng V, Ericksen RE, et al. Identification of a bone marrow-derived mesenchymal progenitor cell subset that can contribute to the gastric epithelium. Lab Investig. 2009;89:1410–22.PubMedCrossRef
40.
Quante M, Tu SP, Tomita H, Gonda T, Wang SS, Takashi S, et al. Bone marrow-derived myofibroblasts contribute to the mesenchymal stem cell niche and promote tumor growth. Cancer Cell. 2011;19:257–72.PubMedCrossRef
41.
Shibata W, Ariyama H, Westphalen CB, Worthley DL, Muthupalani S, Asfaha S, et al. Stromal cell-derived factor-1 overexpression induces gastric dysplasia through expansion of stromal myofibroblasts and epithelial progenitors. Gut 2012 [Epub ahead of print].
42.
Varon C, Dubus P, Mazurier F, Asencio C, Chambonnier L, Ferrand J, et al. Helicobacter pylori infection recruits bone marrow-derived cells that participate in gastric preneoplasia in mice. Gastroenterology. 2012;142:281–91.PubMedCrossRef
43.
Marhaba R, Zoller M. CD44 in cancer progression: adhesion, migration and growth regulation. J Mol Histol. 2004;35:211–31.PubMedCrossRef
44.
Zöller M. CD44: can a cancer-initiating cell profit from an abundantly expressed molecule? Nat Rev Cancer. 2011;11:254–67.PubMedCrossRef
45.
Takaishi S, Okumura T, Tu S, Wang SS, Shibata W, Vigneshwaran R, et al. Identification of gastric cancer stem cells using the cell surface marker CD44. Stem Cells. 2009;27:1006–20.PubMedCrossRef
46.
47.
Zhang C, Li C, He F, Cai Y, Yang H. Identification of CD44+CD24+ gastric cancer stem cells. J Cancer Res Clin Oncol. 2011;137:1679–86.PubMedCrossRef
48.
Chen T, Yang K, Yu J, Meng W, Yuan D, Bi F, et al. Identification and expansion of cancer stem cells in tumor tissues and peripheral blood derived from gastric adenocarcinoma patients. Cell Res. 2012;22:248–58.PubMedCrossRef
49.
Han ME, Jeon TY, Hwang SH, Lee YS, Kim HJ, Shim HE, et al. Cancer spheres from gastric cancer patients provide an ideal model system for cancer stem cell research. Cell Mol Life Sci. 2011;68:3589–605.PubMedCrossRef
50.
Jiang J, Zhang Y, Chuai S, Wang Z, Zheng D, Xu F, et al. Trastuzumab (herceptin) targets gastric cancer stem cells characterized by CD90 phenotype. Oncogene. 2012;31:671–82.PubMedCrossRef
51.
Katsuno Y, Ehata S, Yashiro M, Yanagihara K, Hirakawa K, Miyazono K. Coordinated expression of REG4 and aldehyde dehydrogenase 1 regulating tumourigenic capacity of diffuse-type gastric carcinoma-initiating cells is inhibited by TGF-β. J Pathol. 2012;228(3):391–404.PubMedCrossRef
52.
Ohkuma M, Haraguchi N, Ishii H, Mimori K, Tanaka F, Kim HM, et al. Absence of CD71 transferrin receptor characterizes human gastric adenosquamous carcinoma stem cells. Ann Surg Oncol. 2012;19:1357–64.PubMedCrossRef
53.
Quintana E, Shackleton M, Sabel MS, Fullen DR, Johnson TM, Morrison SJ. Efficient tumour formation by single human melanoma cells. Nature. 2008;456:593–8.PubMedCrossRef
54.
Rocco A, Liguori E, Pirozzi G, Tirino V, Compare D, Franco R, et al. CD133 and CD44 cell surface markers do not identify cancer stem cells in primary human gastric tumors. J Cell Physiol. 2012;227:2686–93.PubMedCrossRef
55.
Moserle L, Ghisi M, Amadori A, Indraccolo S. Side population and cancer stem cells: therapeutic implications. Cancer Lett. 2010;288:1–9.PubMedCrossRef
56.
Golebiewska A, Brons NH, Bjerkvig R, Niclou SP. Critical appraisal of the side population assay in stem cell and cancer stem cell research. Cell Stem Cell. 2011;8:136–47.PubMedCrossRef
57.
Hadnagy A, Gaboury L, Beaulieu R, Balicki D. SP analysis may be used to identify cancer stem cell populations. Exp Cell Res. 2006;312:3701–10.PubMedCrossRef
58.
59.
Haraguchi N, Inoue H, Tanaka F, Mimori K, Utsunomiya T, Sasaki A, et al. Cancer stem cells in human gastrointestinal cancers. Hum Cell. 2006;19:24–9.PubMedCrossRef
60.
Haraguchi N, Utsunomiya T, Inoue H, Tanaka F, Mimori K, Barnard GF, et al. Characterization of a side population of cancer cells from human gastrointestinal system. Stem Cells. 2006;24:506–13.PubMedCrossRef
61.
Schmuck R, Warneke V, Behrens HM, Simon E, Weichert W, Röcken C. Genotypic and phenotypic characterization of side population of gastric cancer cell lines. Am J Pathol. 2011;178:1792–804.PubMedCrossRef
62.
Nishii T, Yashiro M, Shinto O, Sawada T, Ohira M, Hirakawa K. Cancer stem cell-like SP cells have a high adhesion ability to the peritoneum in gastric carcinoma. Cancer Sci. 2009;100:1397–402.PubMedCrossRef
63.
Fukuda K, Saikawa Y, Ohashi M, Kumagai K, Kitajima M, Okano H, et al. Tumor initiating potential of side population cells in human gastric cancer. Int J Oncol. 2009;34:1201–7.PubMed
64.
Ehata S, Johansson E, Katayama R, Koike S, Watanabe A, Hoshino Y, et al. Transforming growth factor-β decreases the cancer-initiating cell population within diffuse-type gastric carcinoma cells. Oncogene. 2011;30:1693–705.PubMedCrossRef
65.
Burkert J, Otto WR, Wright NA. Side populations of gastrointestinal cancers are not enriched in stem cells. J Pathol. 2008;214:564–73.PubMedCrossRef
66.
Zhang H, Xi H, Cai A, Xia Q, Wang XX, Lu C, et al. Not all side population cells contain cancer stem-like cells in human gastric cancer cell lines. Dig Dis Sci. 2012 [Epub ahead of print].
67.
Magee JA, Piskounova E, Morrison SJ. Cancer stem cells: impact, heterogeneity, and uncertainty. Cancer Cell. 2012;21:283–96.PubMedCrossRef
68.
Tsujimoto H, Hagiwara A, Shimotsuma M, Sakakura C, Osaki K, Sasaki S, et al. Role of milky spots as selective implantation sites for malignant cells in peritoneal dissemination in mice. J Cancer Res Clin Oncol. 1996;122:590–5.PubMedCrossRef
69.
Berberich S, Dähne S, Schippers A, Peters T, Müller W, Kremmer E, et al. Differential molecular and anatomical basis for B cell migration into the peritoneal cavity and omental milky spots. J Immunol. 2008;180:2196–203.PubMed
70.
Cui L, Johkura K, Liang Y, Teng R, Ogiwara N, Okouchi Y, et al. Biodefense function of omental milky spots through cell adhesion molecules and leukocyte proliferation. Cell Tissue Res. 2002;310:321–30.PubMedCrossRef
71.
Oosterling SJ, van der Bij GJ, Bögels M, van der Sijp JR, Beelen RH, Meijer S, et al. Insufficient ability of omental milky spots to prevent peritoneal tumor outgrowth supports omentectomy in minimal residual disease. Cancer Immunol Immunother. 2006;55:1043–51.PubMedCrossRef
72.
Gerber SA, Rybalko VY, Bigelow CE, Lugade AA, Foster TH, Frelinger JG, et al. Preferential attachment of peritoneal tumor metastases to omental immune aggregates and possible role of a unique vascular microenvironment in metastatic survival and growth. Am J Pathol. 2006;169:1739–52.PubMedCrossRef
73.
Sorensen EW, Gerber SA, Sedlacek AL, Rybalko VY, Chan WM, Lord EM. Omental immune aggregates and tumor metastasis within the peritoneal cavity. Immunol Res. 2009;45:185–94.PubMedCrossRef
74.
Cao L, Hu X, Zhang Y. Omental milky spots—highly efficient “natural filter” for screening gastric cancer stem cells. Med Hypotheses. 2009;73:1017–8.PubMedCrossRef
75.
Cao L, Hu X, Zhang Y, Sun XT. Omental milky spots in screening gastric cancer stem cells. Neoplasma. 2011;58:20–6.PubMedCrossRef
76.
Winquist RJ, Boucher DM, Wood M, Furey BF. Targeting cancer stem cells for more effective therapies: taking out cancer’s locomotive engine. Biochem Pharmacol. 2009;78:326–34.PubMedCrossRef
77.
Takebe N, Harris PJ, Warren RQ, Ivy SP. Targeting cancer stem cells by inhibiting Wnt, Notch, and Hedgehog pathways. Nat Rev Clin Oncol. 2011;8:97–106.PubMedCrossRef
78.
Katoh M. Dysregulation of stem cell signaling network due to germline mutation, SNP, Helicobacter pylori infection, epigenetic change and genetic alteration in gastric cancer. Cancer Biol Ther. 2007;6:832–9.PubMedCrossRef
79.
Eaves CJ, Humphries RK. Acute myeloid leukemia and the Wnt pathway. N Engl J Med. 2010;362:2326–7.PubMedCrossRef
80.
Nusse R, Fuerer C, Ching W, Harnish K, Logan C, Zeng A, et al. Wnt signaling and stem cell control. Cold Spring Harb Symp Quant Biol. 2008;73:59–66.PubMedCrossRef
81.
82.
Vermeulen L, De Sousa EMF, van der Heijden M, Cameron K, de Jong JH, Borovski T, et al. Wnt activity defines colon cancer stem cells and is regulated by the microenvironment. Nat Cell Biol. 2010;12:468–76.PubMedCrossRef
83.
Malanchi I, Peinado H, Kassen D, Hussenet T, Metzger D, Chambon P, et al. Cutaneous cancer stem cell maintenance is dependent on beta-catenin signalling. Nature. 2008;452:650–3.PubMedCrossRef
84.
Oshima H, Matsunaga A, Fujimura T, Tsukamoto T, Taketo MM, Oshima M. Carcinogenesis in mouse stomach by simultaneous activation of the Wnt signaling and prostaglandin E2 pathway. Gastroenterology. 2006;131:1086–95.PubMedCrossRef
85.
Ishimoto T, Oshima H, Oshima M, Kai K, Torii R, Masuko T, et al. CD44+ slow-cycling tumor cell expansion is triggered by cooperative actions of Wnt and prostaglandin E2 in gastric tumorigenesis. Cancer Sci. 2010;101:673–8.PubMedCrossRef
86.
Byun T, Karimi M, Marsh JL, Milovanovic T, Lin F, Holcombe RF. Expression of secreted Wnt antagonists in gastrointestinal tissues: potential role in stem cell homeostasis. J Clin Pathol. 2005;58:515–9.PubMedCrossRef
87.
Cai C, Zhu X. The Wnt/β-catenin pathway regulates self-renewal of cancer stem-like cells in human gastric cancer. Mol Med Rep. 2012;5:1191–6.PubMed
88.
Merchant JL. Hedgehog signalling in gut development, physiology and cancer. J Physiol. 2012;590(Pt 3):421–32.PubMed
89.
van den Brink GR, Hardwick JC, Tytgat GN, Brink MA, Ten Kate FJ, Van Deventer SJ, et al. Sonic hedgehog regulates gastric gland morphogenesis in man and mouse. Gastroenterology. 2001;121:317–8.PubMedCrossRef
90.
Dimmler A, Brabletz T, Hlubek F, Hafner M, Rau T, Kirchner T, et al. Transcription of sonic hedgehog, a potential factor for gastric morphogenesis and gastric mucosa maintenance, is up-regulated in acidic conditions. Lab Investig. 2003;83:1829–37.PubMedCrossRef
91.
Berman DM, Karhadkar SS, Maitra A, Montes De Oca R, Gerstenblith MR, Briggs K, et al. Widespread requirement for Hedgehog ligand stimulation in growth of digestive tract tumors. Nature. 2003;425:846–51.PubMedCrossRef
92.
Ma X, Chen K, Huang S, Zhang X, Adegboyega PA, Evers BM, et al. Frequent activation of the hedgehog pathway in advanced gastric adenocarcinomas. Carcinogenesis. 2005;26:1698–705.PubMedCrossRef
93.
Martin J, Donnelly JM, Houghton J, Zavros Y. The role of sonic hedgehog reemergence during gastric cancer. Dig Dis Sci. 2010;55:1516–24.PubMedCrossRef
94.
Ohta M, Tateishi K, Kanai F, Watabe H, Kondo S, Guleng B, et al. p53-Independent negative regulation of p21/cyclin-dependent kinase-interacting protein 1 by the sonic hedgehog-glioma-associated oncogene 1 pathway in gastric carcinoma cells. Cancer Res. 2005;65:10822–9.PubMedCrossRef
95.
Fukaya M, Isohata N, Ohta H, Aoyagi K, Ochiya T, Saeki N, et al. Hedgehog signal activation in gastric pit cell and in diffuse-type gastric cancer. Gastroenterology. 2006;131:14–29.PubMedCrossRef
96.
Lee SY, Han HS, Lee KY, Hwang TS, Kim JH, Sung IK, et al. Sonic hedgehog expression in gastric cancer and gastric adenoma. Oncol Rep. 2007;17:1051–5.PubMed
97.
Yoo YA, Kang MH, Kim JS, Oh SC. Sonic hedgehog signaling promotes motility and invasiveness of gastric cancer cells through TGF-beta-mediated activation of the ALK5–Smad 3 pathway. Carcinogenesis. 2008;29:480–90.PubMedCrossRef
98.
Lee KM, Lee JS, Jung HS, Park DK, Park HS, Hahm KB. Late reactivation of sonic hedgehog by Helicobacter pylori results in population of gastric epithelial cells that are resistant to apoptosis: implication for gastric carcinogenesis. Cancer Lett. 2010;287:44–53.PubMedCrossRef
99.
Song Z, Yue W, Wei B, Wang N, Li T, Guan L, et al. Sonic hedgehog pathway is essential for maintenance of cancer stem-like cells in human gastric cancer. PLoS ONE. 2011;6:e17687.PubMedCrossRef
100.
Lai EC. Notch signaling: control of cell communication and cell fate. Development. 2004;131:965–73.PubMedCrossRef
101.
Katoh M, Katoh M. Notch signaling in gastrointestinal tract (review). Int J Oncol. 2007;30:247–51.PubMed
102.
Pannuti A, Foreman K, Rizzo P, Osipo C, Golde T, Osborne B, et al. Targeting Notch to target cancer stem cells. Clin Cancer Res. 2010;16:3141–52.PubMedCrossRef
103.
Kim TH, Shivdasani RA. Notch signaling in stomach epithelial stem cell homeostasis. J Exp Med. 2011;208:677–88.PubMedCrossRef
104.
Purow B. Notch inhibition as a promising new approach to cancer therapy. Adv Exp Med Biol. 2012;727:305–19.PubMedCrossRef
105.
Ji Q, Hao X, Meng Y, Zhang M, Desano J, Fan D, et al. Restoration of tumor suppressor miR-34 inhibits human p53-mutant gastric cancer tumorspheres. BMC Cancer. 2008;8:266.PubMedCrossRef
106.
Yeh TS, Wu CW, Hsu KW, Liao WJ, Yang MC, Li AF, et al. The activated Notch1 signal pathway is associated with gastric cancer progression through cyclooxygenase-2. Cancer Res. 2009;69:5039–48.PubMedCrossRef
107.
Wu WK, Cho CH, Lee CW, Fan D, Wu K, Yu J, et al. Dysregulation of cellular signaling in gastric cancer. Cancer Lett. 2010;295:144–53.PubMedCrossRef
108.
Piazzi G, Fini L, Selgrad M, Garcia M, Daoud Y, Wex T, et al. Epigenetic regulation of Delta-Like1 controls Notch1 activation in gastric cancer. Oncotarget. 2011;2:1291–301.PubMed
109.
Tseng YC, Tsai YH, Tseng MJ, Hsu KW, Yang MC, Huang KH, et al. Notch2-induced COX-2 expression enhancing gastric cancer progression. Mol Carcinog. 2011;51(12):939–51.PubMedCrossRef
110.
Hsu KW, Hsieh RH, Huang KH, Li AF, Chi CW, Wang TY, et al. Activation of the Notch1/STAT3/Twist signaling axis promotes gastric cancer progression. Carcinogenesis. 2012;33(8):1459–67.PubMedCrossRef
111.
Sansone P, Storci G, Giovannini C, Pandolfi S, Pianetti S, Taffurelli M, et al. p66Shc/Notch-3 interplay controls self-renewal and hypoxia survival in human stem/progenitor cells of the mammary gland expanded in vitro as mammospheres. Stem Cells. 2007;25:807–15.PubMedCrossRef
112.
Sikandar SS, Pate KT, Anderson S, Dizon D, Edwards RA, Waterman ML, et al. NOTCH signaling is required for formation and self-renewal of tumor-initiating cells and for repression of secretory cell differentiation in colon cancer. Cancer Res. 2010;70:1469–78.PubMedCrossRef
113.
Fan X, Matsui W, Khaki L, Stearns D, Chun J, Li YM, et al. Notch pathway inhibition depletes stem-like cells and blocks engraftment in embryonal brain tumors. Cancer Res. 2006;66:7445–52.PubMedCrossRef
114.
Fan X, Khaki L, Zhu TS, Soules ME, Talsma CE, Gul N, et al. Notch pathway blockade depletes CD133-positive glioblastoma cells and inhibits growth of tumor neurospheres and xenografts. Stem Cells. 2010;28:5–16.PubMed
115.
Auclair BA, Benoit YD, Rivard N, Mishina Y, Perreault N. Bone morphogenetic protein signaling is essential for terminal differentiation of the intestinal secretory cell lineage. Gastroenterology. 2007;133:887–96.PubMedCrossRef
116.
He XC, Zhang J, Tong WG, Tawfik O, Ross J, Scoville DH, et al. BMP signaling inhibits intestinal stem cell self-renewal through suppression of Wnt–beta-catenin signaling. Nat Genet. 2004;36:1117–21.PubMedCrossRef
117.
Shinohara M, Mao M, Keeley TM, El-Zaatari M, Lee HJ, Eaton KA, Samuelson LC, et al. Bone morphogenetic protein signaling regulates gastric epithelial cell development and proliferation in mice. Gastroenterology. 2010;139(205060):e2.PubMed
118.
Maloum F, Allaire JM, Gagné-Sansfaçon J, Roy E, Belleville K, Sarret P, et al. Epithelial BMP signaling is required for proper specification of epithelial cell lineages and gastric endocrine cells. Am J Physiol Gastrointest Liver Physiol. 2011;300:G1065–79.PubMedCrossRef
119.
Wen XZ, Akiyama Y, Baylin SB, Yuasa Y. Frequent epigenetic silencing of the bone morphogenetic protein 2 gene through methylation in gastric carcinomas. Oncogene. 2006;25:2666–73.PubMedCrossRef
120.
Hohenstein P, Molenaar L, Elsinga J, Morreau H, van der Klift H, Struijk A, et al. Serrated adenomas and mixed polyposis caused by a splice acceptor deletion in the mouse Smad4 gene. Genes Chromosomes Cancer. 2003;36:273–82.PubMedCrossRef
121.
Bleuming SA, He XC, Kodach LL, Hardwick JC, Koopman FA, Ten Kate FJ, et al. Bone morphogenetic protein signaling suppresses tumorigenesis at gastric epithelial transition zones in mice. Cancer Res. 2007;67:8149–55.PubMedCrossRef
122.
Wen XZ, Miyake S, Akiyama Y, Yuasa Y. BMP-2 modulates the proliferation and differentiation of normal and cancerous gastric cells. Biochem Biophys Res Commun. 2004;316:100–6.PubMedCrossRef
123.
Zhang J, Ge Y, Sun L, Cao J, Wu Q, Guo L, et al. Effect of bone morphogenetic protein-2 on proliferation and apoptosis of gastric cancer cells. Int J Med Sci. 2012;9:184–92.PubMedCrossRef
124.
Shirai YT, Ehata S, Yashiro M, Yanagihara K, Hirakawa K, Miyazono K. Bone morphogenetic protein-2 and -4 play tumor suppressive roles in human diffuse-type gastric carcinoma. Am J Pathol. 2011;179:2920–30.PubMedCrossRef
125.
Ivanova T, Zouridis H, Wu Y, Cheng LL, Tan IB, Gopalakrishnan V, et al. Integrated epigenomics identifies BMP4 as a modulator of cisplatin sensitivity in gastric cancer. Gut 2012 [Epub ahead of print].
126.
Park Y, Kim JW, Kim DS, Kim EB, Park SJ, Park JY, et al. The bone morphogenesis protein-2 (BMP-2) is associated with progression to metastatic disease in gastric cancer. Cancer Res Treat. 2008;40:127–32.PubMedCrossRef
127.
Park Y, Kang MH, Seo HY, Park JM, Choi CW, Kim YH, et al. Bone morphogenetic protein-2 levels are elevated in the patients with gastric cancer and correlate with disease progression. Med Oncol. 2010;27:1192–9.PubMedCrossRef
128.
Kang MH, Kim JS, Seo JE, Oh SC, Yoo YA. BMP2 accelerates the motility and invasiveness of gastric cancer cells via activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. Exp Cell Res. 2010;316:24–37.PubMedCrossRef
129.
Kang MH, Oh SC, Lee HJ, Kang HN, Kim JL, Kim JS, et al. Metastatic function of BMP-2 in gastric cancer cells: the role of PI3K/AKT, MAPK, the NF-κB pathway, and MMP-9 expression. Exp Cell Res. 2011;317:1746–62.PubMedCrossRef
130.
Aoki M, Ishigami S, Uenosono Y, Arigami T, Uchikado Y, Kita Y, et al. Expression of BMP-7 in human gastric cancer and its clinical significance. Br J Cancer. 2011;104:714–8.PubMedCrossRef
131.
Caja L, Kahata K, Moustakas A. Context-dependent action of transforming growth factor β family members on normal and cancer stem cells. Curr Pharm Des. 2012 [Epub ahead of print].
132.
Kobayashi A, Okuda H, Xing F, Pandey PR, Watabe M, Hirota S, et al. Bone morphogenetic protein 7 in dormancy and metastasis of prostate cancer stem-like cells in bone. J Exp Med. 2011;208:2641–55.PubMedCrossRef
133.
Buijs JT, van der Horst G, van den Hoogen C, Cheung H, de Rooij B, Kroon J, et al. The BMP2/7 heterodimer inhibits the human breast cancer stem cell subpopulation and bone metastases formation. Oncogene. 2012;31:2164–74.PubMedCrossRef
134.
McLean K, Gong Y, Choi Y, Deng N, Yang K, Bai S, et al. Human ovarian carcinoma-associated mesenchymal stem cells regulate cancer stem cells and tumorigenesis via altered BMP production. J Clin Investig. 2011;121:3206–19.PubMedCrossRef
135.
Piccirillo SG, Reynolds BA, Zanetti N, Lamorte G, Binda E, Broggi G, et al. Bone morphogenetic proteins inhibit the tumorigenic potential of human brain tumour-initiating cells. Nature. 2006;444:761–5.PubMedCrossRef
136.
137.
Borovski T, De Sousa E, Melo F, Vermeulen L, Medema JP. Cancer stem cell niche: the place to be. Cancer Res. 2011;71:634–9.PubMedCrossRef
138.
Hovinga KE, Shimizu F, Wang R, Panagiotakos G, Van Der Heijden M, Moayedpardazi H, et al. Inhibition of Notch signaling in glioblastoma targets cancer stem cells via an endothelial cell intermediate. Stem Cells. 2010;28:1019–29.PubMedCrossRef
139.
Folkins C, Man S, Xu P, Shaked Y, Hicklin DJ, Kerbel RS. Anticancer therapies combining antiangiogenic and tumor cell cytotoxic effects reduce the tumor stem-like cell fraction in glioma xenograft tumors. Cancer Res. 2007;67:3560–4.PubMedCrossRef
140.
Guo X, Oshima H, Kitmura T, Taketo MM, Oshima M. Stromal fibroblasts activated by tumor cells promote angiogenesis in mouse gastric cancer. J Biol Chem. 2008;283:19864–71.PubMedCrossRef
141.
Worthley DL, Ruszkiewicz A, Davies R, Moore S, Nivison-Smith I, Bik To L, et al. Human gastrointestinal neoplasia-associated myofibroblasts can develop from bone marrow-derived cells following allogeneic stem cell transplantation. Stem Cells. 2009;27:1463–8.PubMedCrossRef
142.
Soeda A, Park M, Lee D, Mintz A, Androutsellis-Theotokis A, McKay RD, et al. Hypoxia promotes expansion of the CD133-positive glioma stem cells through activation of HIF-1alpha. Oncogene. 2009;28:3949–59.PubMedCrossRef
143.
Seidel S, Garvalov BK, Wirta V, von Stechow L, Schänzer A, Meletis K, et al. A hypoxic niche regulates glioblastoma stem cells through hypoxia inducible factor 2 alpha. Brain. 2010;133(Pt 4):983–95.PubMedCrossRef
144.
Liang D, Ma Y, Liu J, Trope CG, Holm R, Nesland JM, et al. The hypoxic microenvironment upgrades stem-like properties of ovarian cancer cells. BMC Cancer. 2012;12:201.PubMedCrossRef
145.
Ma Y, Liang D, Liu J, Axcrona K, Kvalheim G, Stokke T, et al. Prostate cancer cell lines under hypoxia exhibit greater stem-like properties. PLoS ONE. 2011;6:e29170.PubMedCrossRef
146.
Yeung TM, Gandhi SC, Bodmer WF. Hypoxia and lineage specification of cell line-derived colorectal cancer stem cells. Proc Natl Acad Sci USA. 2011;108:4382–7.PubMedCrossRef
147.
Liu L, Ning X, Sun L, Zhang H, Shi Y, Guo C, et al. Hypoxia-inducible factor-1 alpha contributes to hypoxia-induced chemoresistance in gastric cancer. Cancer Sci. 2008;99:121–8.PubMed
148.
Kato Y, Yashiro M, Fuyuhiro Y, Kashiwagi S, Matsuoka J, Hirakawa T, et al. Effects of acute and chronic hypoxia on the radiosensitivity of gastric and esophageal cancer cells. Anticancer Res. 2011;31:3369–75.PubMed
149.
Matsumoto K, Arao T, Tanaka K, Kaneda H, Kudo K, Fujita Y, et al. mTOR signal and hypoxia-inducible factor-1 alpha regulate CD133 expression in cancer cells. Cancer Res. 2009;69:7160–4.PubMedCrossRef
150.
Komuro A, Yashiro M, Iwata C, Morishita Y, Johansson E, Matsumoto Y, et al. Diffuse-type gastric carcinoma: progression, angiogenesis, and transforming growth factor beta signaling. J Natl Cancer Inst. 2009;101:592–604.PubMedCrossRef
151.
Johansson E, Komuro A, Iwata C, Hagiwara A, Fuse Y, Watanabe A, et al. Exogenous introduction of tissue inhibitor of metalloproteinase 2 reduces accelerated growth of TGF-β-disrupted diffuse-type gastric carcinoma. Cancer Sci. 2010;101:2398–403.PubMedCrossRef
152.
Calabrese C, Poppleton H, Kocak M, Hogg TL, Fuller C, Hamner B, et al. A perivascular niche for brain tumor stem cells. Cancer Cell. 2007;11:69–82.PubMedCrossRef
153.
Beck B, Driessens G, Goossens S, Youssef KK, Kuchnio A, Caauwe A, et al. A vascular niche and a VEGF-Nrp1 loop regulate the initiation and stemness of skin tumours. Nature. 2011;478:399–403.PubMedCrossRef
154.
Zhao Y, Bao Q, Renner A, Camaj P, Eichhorn M, Ischenko I, et al. Cancer stem cells and angiogenesis. Int J Dev Biol. 2011;55:477–82.PubMedCrossRef
155.
Ping YF, Bian XW. Concise review: contribution of cancer stem cells to neovascularization. Stem Cells. 2011;29:888–94.PubMedCrossRef
156.
Zhao HC, Qin R, Chen XX, Sheng X, Wu JF, Wang DB, et al. Microvessel density is a prognostic marker of human gastric cancer. World J Gastroenterol. 2006;12:7598–603.PubMed
157.
Kolev Y, Uetake H, Iida S, Ishikawa T, Kawano T, Sugihara K. Prognostic significance of VEGF expression in correlation with COX-2, microvessel density, and clinicopathological characteristics in human gastric carcinoma. Ann Surg Oncol. 2007;14:2738–47.PubMedCrossRef
158.
Lieto E, Ferraraccio F, Orditura M, Castellano P, Mura AL, Pinto M, et al. Expression of vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) is an independent prognostic indicator of worse outcome in gastric cancer patients. Ann Surg Oncol. 2008;15:69–79.PubMedCrossRef
159.
Yang Q, Ye ZY, Zhang JX, Tao HQ, Li SG, Zhao ZS. Expression of matrix metalloproteinase-9 mRNA and vascular endothelial growth factor protein in gastric carcinoma and its relationship to its pathological features and prognosis. Anat Rec (Hoboken). 2010;293:2012–9.CrossRef
160.
Suzuki S, Dobashi Y, Hatakeyama Y, Tajiri R, Fujimura T, Heldin CH, et al. Clinicopathological significance of platelet-derived growth factor (PDGF)-B and vascular endothelial growth factor-A expression, PDGF receptor-β phosphorylation, and microvessel density in gastric cancer. BMC Cancer. 2010;10:659.PubMedCrossRef
161.
Ohtsu A, Shah MA, Van Cutsem E, Rha SY, Sawaki A, Park SR, et al. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study. J Clin Oncol. 2011;29:3968–76.PubMedCrossRef
162.
Van Cutsem E, de Haas S, Kang YK, Ohtsu A, Tebbutt NC, Ming Xu J, Peng Yong W, et al. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a biomarker evaluation from the AVAGAST randomized phase III trial. J Clin Oncol. 2012;30:2119–27.PubMedCrossRef
163.
Petrillo M, Scambia G, Ferrandina G. Novel targets for VEGF-independent anti-angiogenic drugs. Expert Opin Investig Drugs. 2012;21:451–72.PubMedCrossRef
164.
Yao XH, Ping YF, Bian XW. Contribution of cancer stem cells to tumor vasculogenic mimicry. Protein Cell. 2011;2:266–72.PubMedCrossRef
165.
Mirshahi P, Rafii A, Vincent L, Berthaut A, Varin R, Kalantar G, et al. Vasculogenic mimicry of acute leukemic bone marrow stromal cells. Leukemia. 2009;23:1039–48.PubMedCrossRef
166.
Chiao MT, Yang YC, Cheng WY, Shen CC, Ko JL. CD133+ glioblastoma stem-like cells induce vascular mimicry in vivo. Curr Neurovasc Res. 2011;8:210–9.PubMedCrossRef
167.
Liu TJ, Sun BC, Zhao XL, Zhao XM, Sun T, Gu Q, et al. CD133(+) cells with cancer stem cell characteristics associates with vasculogenic mimicry in triple-negative breast cancer. Oncogene 2012 [Epub ahead of print].
168.
Li M, Gu Y, Zhang Z, Zhang S, Zhang D, Saleem AF, et al. Vasculogenic mimicry: a new prognostic sign of gastric adenocarcinoma. Pathol Oncol Res. 2010;16:259–66.PubMedCrossRef
169.
Jiang J, Liu W, Guo X, Zhang R, Zhi Q, Ji J, Zhang J, et al. IRX1 influences peritoneal spreading and metastasis via inhibiting BDKRB2-dependent neovascularization on gastric cancer. Oncogene. 2011;30:4498–508.PubMedCrossRef
170.
171.
Deonarain MP, Kousparou CA, Epenetos AA. Antibodies targeting cancer stem cells: a new paradigm in immunotherapy? MAbs. 2009;1:12–25.PubMedCrossRef
172.
173.
Chen C, Wei Y, Hummel M, Hoffmann TK, Gross M, Kaufmann AM, et al. Evidence for epithelial–mesenchymal transition in cancer stem cells of head and neck squamous cell carcinoma. PLoS ONE. 2011;6:e16466.PubMedCrossRef
174.
Nakamura K, Iinuma H, Aoyagi Y, Shibuya H, Watanabe T. Predictive value of cancer stem-like cells and cancer-associated genetic markers for peritoneal recurrence of colorectal cancer in patients after curative surgery. Oncology. 2010;78:309–15.PubMedCrossRef
175.
Watanabe T, Kobunai T, Yamamoto Y, Ikeuchi H, Matsuda K, Ishihara S, et al. Predicting ulcerative colitis-associated colorectal cancer using reverse-transcription polymerase chain reaction analysis. Clin Colorectal Cancer. 2011;10:134–41.PubMedCrossRef
176.
Shien K, Toyooka S, Ichimura K, Soh J, Furukawa M, Maki Y, et al. Prognostic impact of cancer stem cell-related markers in non-small cell lung cancer patients treated with induction chemoradiotherapy. Lung Cancer. 2012;77:162–7.PubMedCrossRef
Metadata
Title
Cancer stem cells: the ‘heartbeat’ of gastric cancer
Authors
Guihua Xu
Jie Shen
Xiaohui Ou Yang
Masakiyo Sasahara
Xiulan Su
Publication date
01-07-2013
Publisher
Springer Japan
Published in
Journal of Gastroenterology / Issue 7/2013
Print ISSN: 0944-1174
Electronic ISSN: 1435-5922
DOI
https://doi.org/10.1007/s00535-012-0712-y

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