Skip to main content
Top
Published in: Tumor Biology 2/2016

01-02-2016 | Original Article

A new insight into cancer stem cell markers: Could local and circulating cancer stem cell markers correlate in colorectal cancer?

Authors: Alireza Mirzaei, Gholamreza Tavoosidana, Afshin Abdi Rad, Farhad Rezaei, Masoumeh Tavakoli-Yaraki, Azade Amini Kadijani, Ehsan Khalili, Zahra Madjd

Published in: Tumor Biology | Issue 2/2016

Login to get access

Abstract

Cancer stem cell (CSC) markers could serve as potential prognostic procedure. This study is aimed to investigate the local expression of doublecortin-like kinase 1 (DCLK1) and Lgr5 in colorectal cancer tissues (CRC) at both protein and messenger RNA (mRNA) level, followed by providing a comparison of the local and circulating expression pattern of these markers, based on our present and previous study. The mRNA expression level of DCLK1 and Lgr5 was evaluated using comparative real-time PCR method applying 58 fresh tumor tissues and their correspondent normal margins. Immunohistochemistry was applied to analyze the protein expression level of DCLK1 and Lgr5 in paraffin-embedded CRC tissues. The correlation of DCLK1 and Lgr5 expression pattern with clinicopathological characteristics was assessed. A higher mRNA expression level of DCLK1 (3.28-fold change, p < 0.001) and Lgr5 (2.29-fold change, p < 0.001) was observed in CRC fresh tissues compared to the normal adjacent margins, and the expression level was higher in patients with higher grade and stages of disease and patients who underwent neoadjuvant chemoradiotherapy (CRT). The protein expression level of DCLK1 and Lgr5 was also increased significantly in tumor tissues compared to normal colon tissues which were positively correlated to tumor stage and grade and neoadjuvant CRT. Taken together, the results of protein analysis were in accordance with mRNA assessment. The local expression pattern of DCLK1 and Lgr5 was also in accordance with their expression level in circulation. However, some minor inconsistencies were observed which may be attributed to several factors including the possible effect of CRT on CSC reprogramming.
Literature
1.
go back to reference Allegra A, Alonci A, Penna G, Innao V, Gerace D, Rotondo F, et al. The cancer stem cell hypothesis: a guide to potential molecular targets. Cancer Investig. 2014;32(9):470–95.CrossRef Allegra A, Alonci A, Penna G, Innao V, Gerace D, Rotondo F, et al. The cancer stem cell hypothesis: a guide to potential molecular targets. Cancer Investig. 2014;32(9):470–95.CrossRef
2.
go back to reference Foreman KE, Rizzo P, Osipo C, Miele L. The cancer stem cell hypothesis. Stem Cells and Cancer: Springer; 2009. p. 3–14.CrossRef Foreman KE, Rizzo P, Osipo C, Miele L. The cancer stem cell hypothesis. Stem Cells and Cancer: Springer; 2009. p. 3–14.CrossRef
3.
go back to reference Gil J, Stembalska A, Pesz KA, Sąsiadek MM. Cancer stem cells: the theory and perspectives in cancer therapy. J Appl Genet. 2008;49(2):193–9.CrossRefPubMed Gil J, Stembalska A, Pesz KA, Sąsiadek MM. Cancer stem cells: the theory and perspectives in cancer therapy. J Appl Genet. 2008;49(2):193–9.CrossRefPubMed
5.
go back to reference Pantic I. Cancer stem cell hypotheses: impact on modern molecular physiology and pharmacology research. J Biosci. 2011;36(5):957–61.CrossRefPubMed Pantic I. Cancer stem cell hypotheses: impact on modern molecular physiology and pharmacology research. J Biosci. 2011;36(5):957–61.CrossRefPubMed
7.
go back to reference Tan BT, Park CY, Ailles LE, Weissman IL. The cancer stem cell hypothesis: a work in progress. Lab Investig. 2006;86(12):1203–7.CrossRefPubMed Tan BT, Park CY, Ailles LE, Weissman IL. The cancer stem cell hypothesis: a work in progress. Lab Investig. 2006;86(12):1203–7.CrossRefPubMed
8.
go back to reference Al-Hajj M, Becker MW, Wicha M, Weissman I, Clarke MF. Therapeutic implications of cancer stem cells. Curr Opin Genet Dev. 2004;14(1):43–7.CrossRefPubMed Al-Hajj M, Becker MW, Wicha M, Weissman I, Clarke MF. Therapeutic implications of cancer stem cells. Curr Opin Genet Dev. 2004;14(1):43–7.CrossRefPubMed
9.
go back to reference Bao S, Wu Q, Sathornsumetee S, Hao Y, Li Z, Hjelmeland AB, et al. Stem cell-like glioma cells promote tumor angiogenesis through vascular endothelial growth factor. Cancer Res. 2006;66(16):7843–8.CrossRefPubMed Bao S, Wu Q, Sathornsumetee S, Hao Y, Li Z, Hjelmeland AB, et al. Stem cell-like glioma cells promote tumor angiogenesis through vascular endothelial growth factor. Cancer Res. 2006;66(16):7843–8.CrossRefPubMed
10.
go back to reference 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(3):313–23.CrossRefPubMed 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(3):313–23.CrossRefPubMed
11.
go back to reference Todaro M, Alea MP, Di Stefano AB, Cammareri P, Vermeulen L, Iovino F, et al. Colon cancer stem cells dictate tumor growth and resist cell death by production of interleukin-4. Cell Stem Cell. 2007;1(4):389–402.CrossRefPubMed Todaro M, Alea MP, Di Stefano AB, Cammareri P, Vermeulen L, Iovino F, et al. Colon cancer stem cells dictate tumor growth and resist cell death by production of interleukin-4. Cell Stem Cell. 2007;1(4):389–402.CrossRefPubMed
13.
go back to reference Natarajan TG, FitzGerald KT. Markers in normal and cancer stem cells. Cancer Biomarkers. 2007;3(4):211–31.CrossRefPubMed Natarajan TG, FitzGerald KT. Markers in normal and cancer stem cells. Cancer Biomarkers. 2007;3(4):211–31.CrossRefPubMed
14.
go back to reference Shackleton M, Quintana E, Fearon ER, Morrison SJ. Heterogeneity in cancer: cancer stem cells versus clonal evolution. Cell. 2009;138(5):822–9.CrossRefPubMed Shackleton M, Quintana E, Fearon ER, Morrison SJ. Heterogeneity in cancer: cancer stem cells versus clonal evolution. Cell. 2009;138(5):822–9.CrossRefPubMed
16.
go back to reference Barker N, van Es JH, Kuipers J, Kujala P, van den Born M, Cozijnsen M, et al. Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature. 2007;449(7165):1003–7.CrossRefPubMed Barker N, van Es JH, Kuipers J, Kujala P, van den Born M, Cozijnsen M, et al. Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature. 2007;449(7165):1003–7.CrossRefPubMed
17.
go back to reference Merlos-Suárez A, Barriga FM, Jung P, Iglesias M, Céspedes MV, Rossell D, et al. The intestinal stem cell signature identifies colorectal cancer stem cells and predicts disease relapse. Cell Stem Cell. 2011;8(5):511–24.CrossRefPubMed Merlos-Suárez A, Barriga FM, Jung P, Iglesias M, Céspedes MV, Rossell D, et al. The intestinal stem cell signature identifies colorectal cancer stem cells and predicts disease relapse. Cell Stem Cell. 2011;8(5):511–24.CrossRefPubMed
18.
go back to reference Kemper K, Prasetyanti PR, De Lau W, Rodermond H, Clevers H, Medema JP. Monoclonal antibodies against Lgr5 identify human colorectal cancer stem cells. Stem Cells. 2012;30(11):2378–86.CrossRefPubMed Kemper K, Prasetyanti PR, De Lau W, Rodermond H, Clevers H, Medema JP. Monoclonal antibodies against Lgr5 identify human colorectal cancer stem cells. Stem Cells. 2012;30(11):2378–86.CrossRefPubMed
19.
go back to reference Bellows CF, Gagliardi G. DCLK1 expression in gastrointestinal stem cells and neoplasia. J Cancer Therapeutics Res. 2012;1(1):12.CrossRef Bellows CF, Gagliardi G. DCLK1 expression in gastrointestinal stem cells and neoplasia. J Cancer Therapeutics Res. 2012;1(1):12.CrossRef
20.
go back to reference Li L, Bellows CF. Doublecortin-like kinase 1 exhibits cancer stem cell-like characteristics in a human colon cancer cell line. Chin J Cancer Res. 2013;25(2):134.PubMedPubMedCentral Li L, Bellows CF. Doublecortin-like kinase 1 exhibits cancer stem cell-like characteristics in a human colon cancer cell line. Chin J Cancer Res. 2013;25(2):134.PubMedPubMedCentral
21.
go back to reference Sarkar S, O’Connell M, Kantara C, Singh P. A sub-set of DCLK1+ ve colon cancer stem cells (CSCs) survive curcumin induced autophagy, while co-treatment with curcumin + DCLK1-siRNA eliminates CSCs: Role of long and short isofoms of DCLK1. Cancer Res. 2014;74(19 Supplement):3903.CrossRef Sarkar S, O’Connell M, Kantara C, Singh P. A sub-set of DCLK1+ ve colon cancer stem cells (CSCs) survive curcumin induced autophagy, while co-treatment with curcumin + DCLK1-siRNA eliminates CSCs: Role of long and short isofoms of DCLK1. Cancer Res. 2014;74(19 Supplement):3903.CrossRef
22.
go back to reference Mirzaei A, Tavoosidana G, Modarressi MH, Rad AA, Fazeli MS, Shirkoohi R, et al. Upregulation of circulating cancer stem cell marker, DCLK1 but not Lgr5, in chemoradiotherapy-treated colorectal cancer patients. Tumor Biol. 2015;36(6):1–10.CrossRef Mirzaei A, Tavoosidana G, Modarressi MH, Rad AA, Fazeli MS, Shirkoohi R, et al. Upregulation of circulating cancer stem cell marker, DCLK1 but not Lgr5, in chemoradiotherapy-treated colorectal cancer patients. Tumor Biol. 2015;36(6):1–10.CrossRef
23.
go back to reference Valladares-Ayerbes M, Blanco-Calvo M, Reboredo M, Lorenzo-Patiño MJ, Iglesias-Díaz P, Haz M, et al. Evaluation of the adenocarcinoma-associated gene AGR2 and the intestinal stem cell marker LGR5 as biomarkers in colorectal cancer. Int J Mol Sci. 2012;13(4):4367–87.CrossRefPubMedPubMedCentral Valladares-Ayerbes M, Blanco-Calvo M, Reboredo M, Lorenzo-Patiño MJ, Iglesias-Díaz P, Haz M, et al. Evaluation of the adenocarcinoma-associated gene AGR2 and the intestinal stem cell marker LGR5 as biomarkers in colorectal cancer. Int J Mol Sci. 2012;13(4):4367–87.CrossRefPubMedPubMedCentral
24.
go back to reference Nakanishi Y, Seno H, Fukuoka A, Ueo T, Yamaga Y, Maruno T, et al. Dclk1 distinguishes between tumor and normal stem cells in the intestine. Nat Genet. 2013;45(1):98–103.CrossRefPubMed Nakanishi Y, Seno H, Fukuoka A, Ueo T, Yamaga Y, Maruno T, et al. Dclk1 distinguishes between tumor and normal stem cells in the intestine. Nat Genet. 2013;45(1):98–103.CrossRefPubMed
25.
go back to reference Spiessl B, Beahrs OH, Hermanek P, Hutter R, Scheibe O, Sobin L, et al. TNM atlas: illustrated guide to the TNM/pTNM-classification of malignant tumours: Springer Science & Business Media; 2013. Spiessl B, Beahrs OH, Hermanek P, Hutter R, Scheibe O, Sobin L, et al. TNM atlas: illustrated guide to the TNM/pTNM-classification of malignant tumours: Springer Science & Business Media; 2013.
26.
go back to reference Gunderson LL, Haddock MG, Schild SE. Rectal cancer: preoperative versus postoperative irradiation as a component of adjuvant treatment. Semin Radiat Oncol. 2003;13(4):419–32.CrossRefPubMed Gunderson LL, Haddock MG, Schild SE. Rectal cancer: preoperative versus postoperative irradiation as a component of adjuvant treatment. Semin Radiat Oncol. 2003;13(4):419–32.CrossRefPubMed
27.
go back to reference Sauer R, Liersch T, Merkel S, Fietkau R, Hohenberger W, Hess C, et al. Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years. J Clin Oncol. 2012;30(16):1926–33.CrossRefPubMed Sauer R, Liersch T, Merkel S, Fietkau R, Hohenberger W, Hess C, et al. Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years. J Clin Oncol. 2012;30(16):1926–33.CrossRefPubMed
28.
go back to reference Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative CT method. Nat Protoc. 2008;3(6):1101–8.CrossRefPubMed Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative CT method. Nat Protoc. 2008;3(6):1101–8.CrossRefPubMed
30.
go back to reference Madjd Z, Akbari ME, Zarnani AH, Khayamzadeh M, Kalantari E, Mojtabavi N. Expression of EMSY, a novel BRCA2-link protein, is associated with lymph node metastasis and increased tumor size in breast carcinomas. Asian Pac J Cancer Prev. 2014;15(4):1783–9.CrossRefPubMed Madjd Z, Akbari ME, Zarnani AH, Khayamzadeh M, Kalantari E, Mojtabavi N. Expression of EMSY, a novel BRCA2-link protein, is associated with lymph node metastasis and increased tumor size in breast carcinomas. Asian Pac J Cancer Prev. 2014;15(4):1783–9.CrossRefPubMed
31.
go back to reference Mohsenzadegan M, Madjd Z, Asgari M, Abolhasani M, Shekarabi M, Taeb J, et al. Reduced expression of NGEP is associated with high-grade prostate cancers: a tissue microarray analysis. Cancer Immunol Immunother. 2013;62(10):1609–18.CrossRefPubMed Mohsenzadegan M, Madjd Z, Asgari M, Abolhasani M, Shekarabi M, Taeb J, et al. Reduced expression of NGEP is associated with high-grade prostate cancers: a tissue microarray analysis. Cancer Immunol Immunother. 2013;62(10):1609–18.CrossRefPubMed
32.
go back to reference Sotoudeh K, Hashemi F, Madjd Z, Sadeghipour A, Molanaei S, Kalantary E. The clinicopathologic association of c-MET overexpression in Iranian gastric carcinomas: an immunohistochemical study of tissue microarrays. Diagn Pathol. 2012;7:57.CrossRefPubMedPubMedCentral Sotoudeh K, Hashemi F, Madjd Z, Sadeghipour A, Molanaei S, Kalantary E. The clinicopathologic association of c-MET overexpression in Iranian gastric carcinomas: an immunohistochemical study of tissue microarrays. Diagn Pathol. 2012;7:57.CrossRefPubMedPubMedCentral
33.
go back to reference Detre S, Jotti GS, Dowsett M. A “quickscore” method for immunohistochemical semiquantitation: validation for oestrogen receptor in breast carcinomas. J Clin Pathol. 1995;48(9):876–8.CrossRefPubMedPubMedCentral Detre S, Jotti GS, Dowsett M. A “quickscore” method for immunohistochemical semiquantitation: validation for oestrogen receptor in breast carcinomas. J Clin Pathol. 1995;48(9):876–8.CrossRefPubMedPubMedCentral
34.
go back to reference Schepers AG, Snippert HJ, Stange DE, van den Born M, van Es JH, van de Wetering M, et al. Lineage tracing reveals Lgr5+ stem cell activity in mouse intestinal adenomas. Science. 2012;337(6095):730–5.CrossRefPubMed Schepers AG, Snippert HJ, Stange DE, van den Born M, van Es JH, van de Wetering M, et al. Lineage tracing reveals Lgr5+ stem cell activity in mouse intestinal adenomas. Science. 2012;337(6095):730–5.CrossRefPubMed
36.
go back to reference Saqui-Salces M, Keeley TM, Grosse AS, Qiao XT, El-Zaatari M, Gumucio DL, et al. Gastric tuft cells express DCLK1 and are expanded in hyperplasia. Histochem Cell Biol. 2011;136(2):191–204.CrossRefPubMedPubMedCentral Saqui-Salces M, Keeley TM, Grosse AS, Qiao XT, El-Zaatari M, Gumucio DL, et al. Gastric tuft cells express DCLK1 and are expanded in hyperplasia. Histochem Cell Biol. 2011;136(2):191–204.CrossRefPubMedPubMedCentral
37.
go back to reference Takeda K, Kinoshita I, Shimizu Y, Matsuno Y, Shichinohe T, Dosaka-Akita H. Expression of LGR5, an intestinal stem cell marker, during each stage of colorectal tumorigenesis. Anticancer Res. 2011;31(1):263–70.PubMed Takeda K, Kinoshita I, Shimizu Y, Matsuno Y, Shichinohe T, Dosaka-Akita H. Expression of LGR5, an intestinal stem cell marker, during each stage of colorectal tumorigenesis. Anticancer Res. 2011;31(1):263–70.PubMed
38.
go back to reference Wu X-S, Xi H-Q, Chen L. Lgr5 is a potential marker of colorectal carcinoma stem cells that correlates with patient survival. World J Surg Oncol. 2012;10(1):244.CrossRefPubMedPubMedCentral Wu X-S, Xi H-Q, Chen L. Lgr5 is a potential marker of colorectal carcinoma stem cells that correlates with patient survival. World J Surg Oncol. 2012;10(1):244.CrossRefPubMedPubMedCentral
39.
go back to reference Meng Q, Yu J, Kang W, Ma Z, Zhou W, Li J, et al. Expression of doublecortin-like kinase 1 in human gastric cancer and its correlation with prognosis. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2013;35(6):639–44.PubMed Meng Q, Yu J, Kang W, Ma Z, Zhou W, Li J, et al. Expression of doublecortin-like kinase 1 in human gastric cancer and its correlation with prognosis. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2013;35(6):639–44.PubMed
40.
41.
42.
go back to reference Guo Y, Xiao P, Lei S, Deng F, Xiao GG, Liu Y, et al. How is mRNA expression predictive for protein expression? A correlation study on human circulating monocytes. Acta Biochim Biophys Sin. 2008;40(5):426–36.CrossRefPubMed Guo Y, Xiao P, Lei S, Deng F, Xiao GG, Liu Y, et al. How is mRNA expression predictive for protein expression? A correlation study on human circulating monocytes. Acta Biochim Biophys Sin. 2008;40(5):426–36.CrossRefPubMed
43.
go back to reference Chen G, Gharib TG, Huang C-C, Taylor JM, Misek DE, Kardia SL, et al. Discordant protein and mRNA expression in lung adenocarcinomas. Mol Cell Proteomics. 2002;1(4):304–13.CrossRefPubMed Chen G, Gharib TG, Huang C-C, Taylor JM, Misek DE, Kardia SL, et al. Discordant protein and mRNA expression in lung adenocarcinomas. Mol Cell Proteomics. 2002;1(4):304–13.CrossRefPubMed
44.
go back to reference Marusyk A, Polyak K. Tumor heterogeneity: causes and consequences. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer. 2010;1805(1):105–17.CrossRef Marusyk A, Polyak K. Tumor heterogeneity: causes and consequences. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer. 2010;1805(1):105–17.CrossRef
45.
go back to reference Valencia-Sanchez MA, Liu J, Hannon GJ, Parker R. Control of translation and mRNA degradation by miRNAs and siRNAs. Genes Dev. 2006;20(5):515–24.CrossRefPubMed Valencia-Sanchez MA, Liu J, Hannon GJ, Parker R. Control of translation and mRNA degradation by miRNAs and siRNAs. Genes Dev. 2006;20(5):515–24.CrossRefPubMed
46.
go back to reference Fabbri M, Calin GA. Epigenetics and miRNAs in human cancer. Adv Genet. 2010;70:87–99.PubMed Fabbri M, Calin GA. Epigenetics and miRNAs in human cancer. Adv Genet. 2010;70:87–99.PubMed
48.
go back to reference Dylla SJ, Beviglia L, Park I-K, Chartier C, Raval J, Ngan L, et al. Colorectal cancer stem cells are enriched in xenogeneic tumors following chemotherapy. PLoS One. 2008;3(6):e2428.CrossRefPubMedPubMedCentral Dylla SJ, Beviglia L, Park I-K, Chartier C, Raval J, Ngan L, et al. Colorectal cancer stem cells are enriched in xenogeneic tumors following chemotherapy. PLoS One. 2008;3(6):e2428.CrossRefPubMedPubMedCentral
49.
go back to reference Wang L, Huang X, Zheng X, Wang X, Li S, Zhang L, et al. Enrichment of prostate cancer stem-like cells from human prostate cancer cell lines by culture in serum-free medium and chemoradiotherapy. Int J Biol Sci. 2013;9(5):472.CrossRefPubMedPubMedCentral Wang L, Huang X, Zheng X, Wang X, Li S, Zhang L, et al. Enrichment of prostate cancer stem-like cells from human prostate cancer cell lines by culture in serum-free medium and chemoradiotherapy. Int J Biol Sci. 2013;9(5):472.CrossRefPubMedPubMedCentral
50.
go back to reference Zhang H, Chang W, Li X, Zhang N, Kong J, Wang Y. Liver cancer stem cells are selectively enriched by low-dose cisplatin. Braz J Med Biol Res. 2014;47(6):478–82.CrossRefPubMedPubMedCentral Zhang H, Chang W, Li X, Zhang N, Kong J, Wang Y. Liver cancer stem cells are selectively enriched by low-dose cisplatin. Braz J Med Biol Res. 2014;47(6):478–82.CrossRefPubMedPubMedCentral
51.
go back to reference Denisov EV, Litviakov NV, Zavyalova MV, Perelmuter VM, Vtorushin SV, Tsyganov MM, et al. Intratumoral morphological heterogeneity of breast cancer: neoadjuvant chemotherapy efficiency and multidrug resistance gene expression. Scientific Reports. 2014;14(4):4709. Denisov EV, Litviakov NV, Zavyalova MV, Perelmuter VM, Vtorushin SV, Tsyganov MM, et al. Intratumoral morphological heterogeneity of breast cancer: neoadjuvant chemotherapy efficiency and multidrug resistance gene expression. Scientific Reports. 2014;14(4):4709.
52.
go back to reference Shah AN, Summy JM, Zhang J, Park SI, Parikh NU, Gallick GE. Development and characterization of gemcitabine-resistant pancreatic tumor cells. Ann Surg Oncol. 2007;14(12):3629–37.CrossRefPubMed Shah AN, Summy JM, Zhang J, Park SI, Parikh NU, Gallick GE. Development and characterization of gemcitabine-resistant pancreatic tumor cells. Ann Surg Oncol. 2007;14(12):3629–37.CrossRefPubMed
53.
go back to reference Yang G, Lu X, Fu H, Jin L, Yao L, Lu Z. Chemotherapy not only enriches but also induces cancer stem cells. Bioscience Hypotheses. 2009;2(6):393–5.CrossRef Yang G, Lu X, Fu H, Jin L, Yao L, Lu Z. Chemotherapy not only enriches but also induces cancer stem cells. Bioscience Hypotheses. 2009;2(6):393–5.CrossRef
54.
go back to reference Muñoz P, Iliou MS, Esteller M. Epigenetic alterations involved in cancer stem cell reprogramming. Mol Oncology. 2012;6(6):620–36.CrossRef Muñoz P, Iliou MS, Esteller M. Epigenetic alterations involved in cancer stem cell reprogramming. Mol Oncology. 2012;6(6):620–36.CrossRef
55.
go back to reference Hollier BG, Evans K, Mani SA. The epithelial-to-mesenchymal transition and cancer stem cells: a coalition against cancer therapies. J Mammary Gland Biol Neoplasia. 2009;14(1):29–43.CrossRefPubMed Hollier BG, Evans K, Mani SA. The epithelial-to-mesenchymal transition and cancer stem cells: a coalition against cancer therapies. J Mammary Gland Biol Neoplasia. 2009;14(1):29–43.CrossRefPubMed
56.
go back to reference Mani SA, Guo W, Liao M-J, Eaton EN, Ayyanan A, Zhou AY, et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 2008;133(4):704–15.CrossRefPubMedPubMedCentral Mani SA, Guo W, Liao M-J, Eaton EN, Ayyanan A, Zhou AY, et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 2008;133(4):704–15.CrossRefPubMedPubMedCentral
57.
go back to reference Polyak K, Weinberg RA. Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits. Nat Rev Cancer. 2009;9(4):265–73.CrossRefPubMed Polyak K, Weinberg RA. Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits. Nat Rev Cancer. 2009;9(4):265–73.CrossRefPubMed
58.
go back to reference Plaks V, Kong N, Werb Z. The cancer stem cell niche: how essential is the niche in regulating stemness of tumor cells? Cell Stem Cell. 2015;16(3):225–38.CrossRefPubMedPubMedCentral Plaks V, Kong N, Werb Z. The cancer stem cell niche: how essential is the niche in regulating stemness of tumor cells? Cell Stem Cell. 2015;16(3):225–38.CrossRefPubMedPubMedCentral
Metadata
Title
A new insight into cancer stem cell markers: Could local and circulating cancer stem cell markers correlate in colorectal cancer?
Authors
Alireza Mirzaei
Gholamreza Tavoosidana
Afshin Abdi Rad
Farhad Rezaei
Masoumeh Tavakoli-Yaraki
Azade Amini Kadijani
Ehsan Khalili
Zahra Madjd
Publication date
01-02-2016
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 2/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-3989-7

Other articles of this Issue 2/2016

Tumor Biology 2/2016 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine