Skip to main content
Top
Published in: Tumor Biology 3/2016

01-03-2016 | Original Article

Role of Helicobacter pylori on cancer of human adipose-derived mesenchymal stem cells and metastasis of tumor cells—an in vitro study

Authors: Sadegh Lotfalah Moradi, Gita Eslami, Hossein Goudarzi, Zahra Hajishafieeha, Masoud Soleimani, Adel Mohammadzadeh, Abdolreza Ardeshirylajimi

Published in: Tumor Biology | Issue 3/2016

Login to get access

Abstract

Recent studies have shown that Helicobacter pylori has a special role in tropism of mesenchymal stem cells (MSCs) towards gastric tissues. This study aimed to find the effects of H. pylori on human adipose-derived mesenchymal stem cells (hA-MSCs) transforming toward cancer cells and also metastasis of tumor cells by synergic effects of H. pylori and gastric epithelial cells (AGS) on MSCs. The expressions of p53, bcl-2, MMP-2, and MMP-9 were examined in hA-MSCs by qRT-PCR technique. Our results demonstrated that H. pylori tries to improve the hA-MSCs carcinogenic activities by overexpression of bcl2 gene as an anti-apoptosis agent against the p53 gene expression as main apoptosis agent. In addition, it showed that H. pylori effects in metastatic activities of hA-MSCs by upregulation of related genes in this process. Perhaps, when hA-MSCs are attracted toward H. pylori chronic or ulcer infected tissues for their tissue healing function, they will be trapped under special gastric microenvironment. We demonstrated the direct and synergic effects of H. pylori in hA-MSCs through alteration of related genes involved in carcinogenesis processes. Hence, understanding of H. pylori-induced molecular pathogenesis could be a powerful strategy not only in identifying the origin and initiation of gastric cancer but also in the treatment of related disease and modification of stem cell therapy methods in the future.
Literature
1.
go back to reference Ferrand J, Lehours P, Schmid-Alliana A, Megraud F, Varon C. Helicobacter pylori infection of gastrointestinal epithelial cells in vitro induces mesenchymal stem cell migration through an NF-kappaB-dependent pathway. PLoS One. 2011;6(12):e29007.CrossRefPubMedPubMedCentral Ferrand J, Lehours P, Schmid-Alliana A, Megraud F, Varon C. Helicobacter pylori infection of gastrointestinal epithelial cells in vitro induces mesenchymal stem cell migration through an NF-kappaB-dependent pathway. PLoS One. 2011;6(12):e29007.CrossRefPubMedPubMedCentral
3.
go back to reference Wilson KT, Crabtree JE. Immunology of helicobacter pylori: insights into the failure of the immune response and perspectives on vaccine studies. Gastroenterology. 2007;133(1):288–308.CrossRefPubMed Wilson KT, Crabtree JE. Immunology of helicobacter pylori: insights into the failure of the immune response and perspectives on vaccine studies. Gastroenterology. 2007;133(1):288–308.CrossRefPubMed
4.
go back to reference Peek RM. Prevention of gastric cancer: when is treatment of helicobacter pylori warranted? Ther Adv Gastroenterol. 2008;1(1):19–31.CrossRef Peek RM. Prevention of gastric cancer: when is treatment of helicobacter pylori warranted? Ther Adv Gastroenterol. 2008;1(1):19–31.CrossRef
5.
go back to reference Mueller A, Falkow S, Amieva MR. Helicobacter pylori and gastric cancer: what can be learned by studying the response of gastric epithelial cells to the infection? Cancer Epidemiol Biomarkers Prev. 2005;14(8):1859–64.CrossRefPubMed Mueller A, Falkow S, Amieva MR. Helicobacter pylori and gastric cancer: what can be learned by studying the response of gastric epithelial cells to the infection? Cancer Epidemiol Biomarkers Prev. 2005;14(8):1859–64.CrossRefPubMed
6.
go back to reference Bessede E, Staedel C, Acuna Amador LA, Nguyen PH, Chambonnier L, Hatakeyama M, et al. Helicobacter pylori generates cells with cancer stem cell properties via epithelial-mesenchymal transition-like changes. Oncogene. 2014;33(32):4123–31.CrossRefPubMed Bessede E, Staedel C, Acuna Amador LA, Nguyen PH, Chambonnier L, Hatakeyama M, et al. Helicobacter pylori generates cells with cancer stem cell properties via epithelial-mesenchymal transition-like changes. Oncogene. 2014;33(32):4123–31.CrossRefPubMed
7.
go back to reference Sterzenbach T, Lee SK, Brenneke B, von Goetz F, Schauer DB, Fox JG, et al. Inhibitory effect of enterohepatic Helicobacter hepaticus on innate immune responses of mouse intestinal epithelial cells. Infect Immun. 2007;75(6):2717–28.CrossRefPubMedPubMedCentral Sterzenbach T, Lee SK, Brenneke B, von Goetz F, Schauer DB, Fox JG, et al. Inhibitory effect of enterohepatic Helicobacter hepaticus on innate immune responses of mouse intestinal epithelial cells. Infect Immun. 2007;75(6):2717–28.CrossRefPubMedPubMedCentral
8.
go back to reference Alzahrani S, Lina TT, Gonzalez J, Pinchuk IV, Beswick EJ, Reyes VE. Effect of Helicobacter pylori on gastric epithelial cells. World J Gastroenterol. 2014;20(36):12767–80.CrossRefPubMedPubMedCentral Alzahrani S, Lina TT, Gonzalez J, Pinchuk IV, Beswick EJ, Reyes VE. Effect of Helicobacter pylori on gastric epithelial cells. World J Gastroenterol. 2014;20(36):12767–80.CrossRefPubMedPubMedCentral
9.
go back to reference Cadamuro AC, Rossi AF, Matos Biselli-Perico J, Fucuta Pereira P, Do Vale EP, Acayaba R, et al. Effect of helicobacter pylori eradication on TLR2 and TLR4 expression in patients with gastric lesions. Mediat Inflamm. 2015;2015:481972.CrossRef Cadamuro AC, Rossi AF, Matos Biselli-Perico J, Fucuta Pereira P, Do Vale EP, Acayaba R, et al. Effect of helicobacter pylori eradication on TLR2 and TLR4 expression in patients with gastric lesions. Mediat Inflamm. 2015;2015:481972.CrossRef
10.
11.
go back to reference Semper RP, Mejias-Luque R, Gross C, Anderl F, Muller A, Vieth M, et al. Helicobacter pylori-induced IL-1beta secretion in innate immune cells is regulated by the NLRP3 inflammasome and requires the cag pathogenicity island. J Immunol. 2014;193(7):3566–76.CrossRefPubMed Semper RP, Mejias-Luque R, Gross C, Anderl F, Muller A, Vieth M, et al. Helicobacter pylori-induced IL-1beta secretion in innate immune cells is regulated by the NLRP3 inflammasome and requires the cag pathogenicity island. J Immunol. 2014;193(7):3566–76.CrossRefPubMed
12.
go back to reference Waldum HL, Kleveland PM, Fossmark R. Upper gastrointestinal physiology and diseases. Scand J Gastroenterol. 2015;50(6):649–656.PubMed Waldum HL, Kleveland PM, Fossmark R. Upper gastrointestinal physiology and diseases. Scand J Gastroenterol. 2015;50(6):649–656.PubMed
13.
go back to reference Wang C, Weber A, Graham DY. Age, period, and cohort effects on gastric cancer mortality. Dig Dis Sci. 2015;60(2):514–23.CrossRefPubMed Wang C, Weber A, Graham DY. Age, period, and cohort effects on gastric cancer mortality. Dig Dis Sci. 2015;60(2):514–23.CrossRefPubMed
14.
15.
go back to reference Eckert MA, Vu Q, Xie K, Yu J, Liao W, Cramer SC, et al. Evidence for high translational potential of mesenchymal stromal cell therapy to improve recovery from ischemic stroke. J Cereb Blood Flow Metab. 2013;33(9):1322–34.CrossRefPubMedPubMedCentral Eckert MA, Vu Q, Xie K, Yu J, Liao W, Cramer SC, et al. Evidence for high translational potential of mesenchymal stromal cell therapy to improve recovery from ischemic stroke. J Cereb Blood Flow Metab. 2013;33(9):1322–34.CrossRefPubMedPubMedCentral
16.
go back to reference Daei-Farshbaf N, Ardeshirylajimi A, Seyedjafari E, Piryaei A, Fadaei Fathabady F, Hedayati M, et al. Bioceramic-collagen scaffolds loaded with human adipose-tissue derived stem cells for bone tissue engineering. Mol Biol Rep. 2014;41(2):741–9.CrossRefPubMed Daei-Farshbaf N, Ardeshirylajimi A, Seyedjafari E, Piryaei A, Fadaei Fathabady F, Hedayati M, et al. Bioceramic-collagen scaffolds loaded with human adipose-tissue derived stem cells for bone tissue engineering. Mol Biol Rep. 2014;41(2):741–9.CrossRefPubMed
17.
go back to reference Donnelly JM, Engevik AC, Engevik M, Schumacher MA, Xiao C, Yang L, et al. Gastritis promotes an activated bone marrow-derived mesenchymal stem cell with a phenotype reminiscent of a cancer-promoting cell. Dig Dis Sci. 2014;59(3):569–82.CrossRefPubMed Donnelly JM, Engevik AC, Engevik M, Schumacher MA, Xiao C, Yang L, et al. Gastritis promotes an activated bone marrow-derived mesenchymal stem cell with a phenotype reminiscent of a cancer-promoting cell. Dig Dis Sci. 2014;59(3):569–82.CrossRefPubMed
18.
go back to reference Mohammadzadeh A, Pourfathollah AA, Shahrokhi S, Hashemi SM, Moradi SL, Soleimani M. Immunomodulatory effects of adipose-derived mesenchymal stem cells on the gene expression of major transcription factors of T cell subsets. Int Immunopharmacol. 2014;20(2):316–21.CrossRefPubMed Mohammadzadeh A, Pourfathollah AA, Shahrokhi S, Hashemi SM, Moradi SL, Soleimani M. Immunomodulatory effects of adipose-derived mesenchymal stem cells on the gene expression of major transcription factors of T cell subsets. Int Immunopharmacol. 2014;20(2):316–21.CrossRefPubMed
19.
go back to reference Ward CL, Sanchez Jr CJ, Pollot BE, Romano DR, Hardy SK, Becerra SC, et al. Soluble factors from biofilms of wound pathogens modulate human bone marrow-derived stromal cell differentiation, migration, angiogenesis, and cytokine secretion. BMC Microbiol. 2015;15(1):75.CrossRefPubMedPubMedCentral Ward CL, Sanchez Jr CJ, Pollot BE, Romano DR, Hardy SK, Becerra SC, et al. Soluble factors from biofilms of wound pathogens modulate human bone marrow-derived stromal cell differentiation, migration, angiogenesis, and cytokine secretion. BMC Microbiol. 2015;15(1):75.CrossRefPubMedPubMedCentral
20.
go back to reference Bussche L, Harman RM, Syracuse BA, Plante EL, Lu YC, Curtis TM, et al. Microencapsulated equine mesenchymal stromal cells promote cutaneous wound healing in vitro. Stem Cell Res Ther. 2015;6(1):66.CrossRefPubMedPubMedCentral Bussche L, Harman RM, Syracuse BA, Plante EL, Lu YC, Curtis TM, et al. Microencapsulated equine mesenchymal stromal cells promote cutaneous wound healing in vitro. Stem Cell Res Ther. 2015;6(1):66.CrossRefPubMedPubMedCentral
21.
go back to reference Rodriguez-Menocal L, Shareef S, Salgado M, Shabbir A, Van Badiavas E. Role of whole bone marrow, whole bone marrow cultured cells, and mesenchymal stem cells in chronic wound healing. Stem Cell Res Ther. 2015;6(1):24.CrossRefPubMedPubMedCentral Rodriguez-Menocal L, Shareef S, Salgado M, Shabbir A, Van Badiavas E. Role of whole bone marrow, whole bone marrow cultured cells, and mesenchymal stem cells in chronic wound healing. Stem Cell Res Ther. 2015;6(1):24.CrossRefPubMedPubMedCentral
22.
go back to reference Correa P, Houghton J. Carcinogenesis of Helicobacter pylori. Gastroenterology. 2007;133(2):659–72.CrossRefPubMed Correa P, Houghton J. Carcinogenesis of Helicobacter pylori. Gastroenterology. 2007;133(2):659–72.CrossRefPubMed
23.
go back to reference Okumura T, Ericksen RE, Takaishi S, Wang SS, Dubeykovskiy Z, Shibata W, et al. K-ras mutation targeted to gastric tissue progenitor cells results in chronic inflammation, an altered microenvironment, and progression to intraepithelial neoplasia. Cancer Res. 2010;70(21):8435–45.CrossRefPubMedPubMedCentral Okumura T, Ericksen RE, Takaishi S, Wang SS, Dubeykovskiy Z, Shibata W, et al. K-ras mutation targeted to gastric tissue progenitor cells results in chronic inflammation, an altered microenvironment, and progression to intraepithelial neoplasia. Cancer Res. 2010;70(21):8435–45.CrossRefPubMedPubMedCentral
24.
go back to reference Luo Y, Liang F, Zhang ZY. PRL1 promotes cell migration and invasion by increasing MMP2 and MMP9 expression through Src and ERK1/2 pathways. Biochemistry. 2009;48(8):1838–46.CrossRefPubMedPubMedCentral Luo Y, Liang F, Zhang ZY. PRL1 promotes cell migration and invasion by increasing MMP2 and MMP9 expression through Src and ERK1/2 pathways. Biochemistry. 2009;48(8):1838–46.CrossRefPubMedPubMedCentral
25.
go back to reference Yan L, Lin B, Gao L, Gao S, Liu C, Wang C, et al. Lewis (y) antigen overexpression increases the expression of MMP-2 and MMP-9 and invasion of human ovarian cancer cells. Int J Mol Sci. 2010;11(11):4441–52.CrossRefPubMedPubMedCentral Yan L, Lin B, Gao L, Gao S, Liu C, Wang C, et al. Lewis (y) antigen overexpression increases the expression of MMP-2 and MMP-9 and invasion of human ovarian cancer cells. Int J Mol Sci. 2010;11(11):4441–52.CrossRefPubMedPubMedCentral
26.
go back to reference Fan HX, Li HX, Chen D, Gao ZX, Zheng JH. Changes in the expression of MMP2, MMP9, and ColIV in stromal cells in oral squamous tongue cell carcinoma: relationships and prognostic implications. J Exp Clin Cancer Res. 2012;31:90.CrossRefPubMedPubMedCentral Fan HX, Li HX, Chen D, Gao ZX, Zheng JH. Changes in the expression of MMP2, MMP9, and ColIV in stromal cells in oral squamous tongue cell carcinoma: relationships and prognostic implications. J Exp Clin Cancer Res. 2012;31:90.CrossRefPubMedPubMedCentral
27.
go back to reference Benassi MS, Gamberi G, Magagnoli G, Molendini L, Ragazzini P, Merli M, et al. Metalloproteinase expression and prognosis in soft tissue sarcomas. Ann Oncol. 2001;12(1):75–80.CrossRefPubMed Benassi MS, Gamberi G, Magagnoli G, Molendini L, Ragazzini P, Merli M, et al. Metalloproteinase expression and prognosis in soft tissue sarcomas. Ann Oncol. 2001;12(1):75–80.CrossRefPubMed
28.
go back to reference Kim HJ, Park CI, Park BW, Lee HD, Jung WH. Expression of MT-1 MMP, MMP2, MMP9 and TIMP2 mRNAs in ductal carcinoma in situ and invasive ductal carcinoma of the breast. Yonsei Med J. 2006;47(3):333–42.CrossRefPubMedPubMedCentral Kim HJ, Park CI, Park BW, Lee HD, Jung WH. Expression of MT-1 MMP, MMP2, MMP9 and TIMP2 mRNAs in ductal carcinoma in situ and invasive ductal carcinoma of the breast. Yonsei Med J. 2006;47(3):333–42.CrossRefPubMedPubMedCentral
29.
go back to reference Khorashadizadeh M, Soleimani M, Khanahmad H, Fallah A, Naderi M, Khorramizadeh M. Bypassing the need for pre-sensitization of cancer cells for anticancer TRAIL therapy with secretion of novel cell penetrable form of Smac from hA-MSCs as cellular delivery vehicle. Tumour Biol. 2015;36(6):4213–21.CrossRefPubMed Khorashadizadeh M, Soleimani M, Khanahmad H, Fallah A, Naderi M, Khorramizadeh M. Bypassing the need for pre-sensitization of cancer cells for anticancer TRAIL therapy with secretion of novel cell penetrable form of Smac from hA-MSCs as cellular delivery vehicle. Tumour Biol. 2015;36(6):4213–21.CrossRefPubMed
30.
go back to reference Li H, Fan X, Kovi RC, Jo Y, Moquin B, Konz R, et al. Spontaneous expression of embryonic factors and p53 point mutations in aged mesenchymal stem cells: a model of age-related tumorigenesis in mice. Cancer Res. 2007;67(22):10889–98.CrossRefPubMed Li H, Fan X, Kovi RC, Jo Y, Moquin B, Konz R, et al. Spontaneous expression of embryonic factors and p53 point mutations in aged mesenchymal stem cells: a model of age-related tumorigenesis in mice. Cancer Res. 2007;67(22):10889–98.CrossRefPubMed
31.
go back to reference Cai X, Stoicov C, Li H, Carlson J, Whary M, Fox JG, et al. Overcoming Fas-mediated apoptosis accelerates Helicobacter-induced gastric cancer in mice. Cancer Res. 2005;65(23):10912–20.CrossRefPubMed Cai X, Stoicov C, Li H, Carlson J, Whary M, Fox JG, et al. Overcoming Fas-mediated apoptosis accelerates Helicobacter-induced gastric cancer in mice. Cancer Res. 2005;65(23):10912–20.CrossRefPubMed
32.
go back to reference Li H, Fan X, Houghton J. Tumor microenvironment: the role of the tumor stroma in cancer. J Cell Biochem. 2007;101(4):805–15.CrossRefPubMed Li H, Fan X, Houghton J. Tumor microenvironment: the role of the tumor stroma in cancer. J Cell Biochem. 2007;101(4):805–15.CrossRefPubMed
33.
go back to reference Li HC, Stoicov C, Rogers AB, Houghton J. Stem cells and cancer: evidence for bone marrow stem cells in epithelial cancers. World J Gastroenterol. 2006;12(3):363–71.CrossRefPubMedPubMedCentral Li HC, Stoicov C, Rogers AB, Houghton J. Stem cells and cancer: evidence for bone marrow stem cells in epithelial cancers. World J Gastroenterol. 2006;12(3):363–71.CrossRefPubMedPubMedCentral
34.
go back to reference Stoicov C, Li H, Carlson J, Houghton J. Bone marrow cells as the origin of stomach cancer. Future Oncol. 2005;1(6):851–62.CrossRefPubMed Stoicov C, Li H, Carlson J, Houghton J. Bone marrow cells as the origin of stomach cancer. Future Oncol. 2005;1(6):851–62.CrossRefPubMed
Metadata
Title
Role of Helicobacter pylori on cancer of human adipose-derived mesenchymal stem cells and metastasis of tumor cells—an in vitro study
Authors
Sadegh Lotfalah Moradi
Gita Eslami
Hossein Goudarzi
Zahra Hajishafieeha
Masoud Soleimani
Adel Mohammadzadeh
Abdolreza Ardeshirylajimi
Publication date
01-03-2016
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 3/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-4137-0

Other articles of this Issue 3/2016

Tumor Biology 3/2016 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