Effect of Helicobacter pylori infection on stromal-derived factor-1/CXCR4 axis in bone marrow-derived mesenchymal stem cells

Authors

1 Kurdistan Molecular & Cellular Research Center, Kurdistan University of Medical Sciences, Sanadaj, Iran

2 Department of Microbiology, Faculty of Medicine, Alborz University of Medical Sciences, Karaj, Iran

3 Department of Physiology, Isfahan Payamnoor University, Isfahan, Iran

Abstract

Background: Recent studies have demonstrated that during chronic Helicobacter pylori (H. pylori) infection bone marrow-derived-mesenchymal stem cells (BMD-MSCs) migrate to the gastric tissue and could be also the origin of gastric adenocarcinoma. The chemokine receptor CXCR4 through binding to its ligand stromal-derived factor (SDF-1) plays a crucial role in migration of inflammatory and stem cells. However, the possible effect of H. pylori infection on the SDF-1/CXCR4 axis has not yet been elucidated.
Materials and Methods: Gastric epithelial cell line, AGS, and BMD-MSCs were cocultured with H. pylori for 24 h. The expression of CXCR4 was examined in BMD-MSCs by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and flow cytometry, and SDF-1 expression in AGS cells was detected by qRT-PCR and enzyme-linked immunosorbent assay. Further, migration of BMD-MSCs toward SDF-1 was evaluated by chemotaxis assay.
Results: We found that coculture of H. pylori with BMD-MSCs or AGS: (i) enhanced CXCR4 expression on the cell surface of BMD-MSCs and (ii) increased SDF-1 secretion by AGS cells. Consistently, we observed that H. pylori-treated BMD-MSCs showed a higher capability to migrate toward SDF-1 gradient compared with untreated cells.
Conclusion: We found that H. pylori upregulates CXCR4 expression in BMD-MSCs and enhance their migration toward SDF-1. This study provides the first evidence that H. pylori infection may enhance BMD-MSCs migration through acting on the SDF-1/CXCR4 axis.

Keywords

1. Jang BG, Kim WH. Molecular pathology of gastric carcinoma. Pathobiology 2011;78:302-10.  Back to cited text no. 1
    
2. Kuipers EJ. Review article: Exploring the link between Helicobacter pylori and gastric cancer. Aliment Pharmacol Ther 1999;1:3-11.  Back to cited text no. 2
    
3. Peek RM Jr., Fiske C, Wilson KT. Role of innate immunity in Helicobacter pylori-induced gastric malignancy. Physiol Rev 2010;90:831-58.  Back to cited text no. 3
    
4. Yasui W, Sentani K, Motoshita J, Nakayama H. Molecular pathobiology of gastric cancer. Scand J Surg 2006;95:225-31.  Back to cited text no. 4
    
5. Hatakeyama M. Helicobacter pylori CagA - A bacterial intruder conspiring gastric carcinogenesis. Int J Cancer 2006;119:1217-23.  Back to cited text no. 5
    
6. Kabir S. Effect of Helicobacter pylori eradication on incidence of gastric cancer in human and animal models: Underlying biochemical and molecular events. Helicobacter 2009;14:159-71.  Back to cited text no. 6
    
7. Farinati F, Cardin R, Cassaro M, Bortolami M, Nitti D, Tieppo C, et alHelicobacter pylori, inflammation, oxidative damage and gastric cancer: A morphological, biological and molecular pathway. Eur J Cancer Prev 2008;17:195-200.  Back to cited text no. 7
    
8. 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.  Back to cited text no. 8
    
9. Hutchinson L, Stenstrom B, Chen D, Piperdi B, Levey S, Lyle S, et al. Human Barrett's adenocarcinoma of the esophagus, associated myofibroblasts, and endothelium can arise from bone marrow-derived cells after allogeneic stem cell transplant. Stem Cells Dev 2011;20:11-7.  Back to cited text no. 9
    
10. Tirode F, Laud-Duval K, Prieur A, Delorme B, Charbord P, Delattre O. Mesenchymal stem cell features of Ewing tumors. Cancer Cell 2007;11:421-9.  Back to cited text no. 10
    
11. 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;12:363-71.  Back to cited text no. 11
    
12. Ingersoll MA, Platt AM, Potteaux S, Randolph GJ. Monocyte trafficking in acute and chronic inflammation. Trends Immunol 2011;32:470-7.  Back to cited text no. 12
    
13. Sun L, Ye RD. Role of G protein-coupled receptors in inflammation. Acta Pharmacol Sin 2012;33:342-50.  Back to cited text no. 13
    
14. Liekens S, Schols D, Hatse S. CXCL12-CXCR4 axis in angiogenesis, metastasis and stem cell mobilization. Curr Pharm Des 2010;16:3903-20.  Back to cited text no. 14
    
15. Zlotnik A, Burkhardt AM, Homey B. Homeostatic chemokine receptors and organ-specific metastasis. Nat Rev Immunol 2011;11:597-606.  Back to cited text no. 15
    
16. Zlotnik A. New insights on the role of CXCR4 in cancer metastasis. J Pathol 2008;215:211-3.  Back to cited text no. 16
    
17. Duda DG, Kozin SV, Kirkpatrick ND, Xu L, Fukumura D, Jain RK. CXCL12 (SDF1α-CXCR4/CXCR7 pathway inhibition: An emerging sensitizer for anticancer therapies? Clin Cancer Res 2011;17:2074-80.  Back to cited text no. 17
    
18. Liu H, Liu S, Li Y, Wang X, Xue W, Ge G, et al. The role of SDF-1-CXCR4/CXCR7 axis in the therapeutic effects of hypoxia-preconditioned mesenchymal stem cells for renal ischemia/reperfusion injury. PLoS One 2012;7:e34608.  Back to cited text no. 18
    
19. Cronin PA, Wang JH, Redmond HP. Hypoxia increases the metastatic ability of breast cancer cells via upregulation of CXCR4. BMC Cancer 2010;10:225.  Back to cited text no. 19
    
20. Lazennec G, Richmond A. Chemokines and chemokine receptors: New insights into cancer-related inflammation. Trends Mol Med 2010;16:133-44.  Back to cited text no. 20
    
21. Zhao C, Lu X, Bu X, Zhang N, Wang W. Involvement of tumor necrosis factor-α in the upregulation of CXCR4 expression in gastric cancer induced by Helicobacter pylori. BMC Cancer 2010;10:1471-2407.  Back to cited text no. 21
    
22. Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc 2008;3:1101-8.  Back to cited text no. 22
    
23. Jalili A, Shirvaikar N, Marquez-Curtis L, Qiu Y, Korol C, Lee H, et al. Fifth complement cascade protein (C5) cleavage fragments disrupt the SDF-1/CXCR4 axis: further evidence that innate immunity orchestrates the mobilization of hematopoietic stem/progenitor cells. Exp Hematol 2010;38:321-32.  Back to cited text no. 23
    
24. Son BR, Marquez-Curtis LA, Kucia M, Wysoczynski M, Turner AR, Ratajczak J, et al. Migration of bone marrow and cord blood mesenchymal stem cells in vitro is regulated by stromal-derived factor-1-CXCR4 and hepatocyte growth factor-c-met axes and involves matrix metalloproteinases. Stem Cells 2006;24:1254-64.  Back to cited text no. 24
    
25. Iwasa S, Yanagawa T, Fan J, Katoh R. Expression of CXCR4 and its ligand SDF-1 in intestinal-type gastric cancer is associated with lymph node and liver metastasis. Anticancer Res 2009;29:4751-8.  Back to cited text no. 25
    
26. Peled A, Grabovsky V, Habler L, Sandbank J, Arenzana-Seisdedos F, Petit I, et al. The chemokine SDF-1 stimulates integrin-mediated arrest of CD34(+) cells on vascular endothelium under shear flow. J Clin Invest 1999;104:1199-211.  Back to cited text no. 26
    
27. Xia XM, Wang FY, Xu WA, Wang ZK, Liu J, Lu YK, et al. CXCR4 antagonist AMD3100 attenuates colonic damage in mice with experimental colitis. World J Gastroenterol 2010;16:2873-80.  Back to cited text no. 27
    
28. Dotan I, Werner L, Vigodman S, Weiss S, Brazowski E, Maharshak N, et al. CXCL12 is a constitutive and inflammatory chemokine in the intestinal immune system. Inflamm Bowel Dis 2010;16:583-92.  Back to cited text no. 28
    
29. 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 2013;62:192-200.  Back to cited text no. 29
    
30. Ferrand J, Lehours P, Schmid-Alliana A, Mégraud F, Varon C. Helicobacter pylori infection of gastrointestinal epithelial cells in vitro induces mesenchymal stem cell migration through an NF- K B-dependent pathway. PLoS One 2011;6:e29007.  Back to cited text no. 30
    
31. Summers C, Rankin SM, Condliffe AM, Singh N, Peters AM, Chilvers ER. Neutrophil kinetics in health and disease. Trends Immunol 2010;31:318-24.  Back to cited text no. 31
    
32. Petit I, Szyper-Kravitz M, Nagler A, Lahav M, Peled A, Habler L, et al. G-CSF induces stem cell mobilization by decreasing bone marrow SDF-1 and up-regulating CXCR4. Nat Immunol 2002;3:687-94.  Back to cited text no. 32
    
33. Avital I, Moreira A, Downey RJ. The origin of epithelial neoplasms after allogeneic stem cell transplantation. Haematologica 2006;91:ELT07; author reply ELT06.  Back to cited text no. 33
    
34. 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 Invest 2009;89:1410-22.  Back to cited text no. 34
    
35. Hu C, Yong X, Li C, Lü M, Liu D, Chen L, et al. CXCL12/CXCR4 axis promotes mesenchymal stem cell mobilization to burn wounds and contributes to wound repair. J Surg Res 2013;183:427-34.  Back to cited text no. 35