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

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 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-MSC migration through acting on the SDF-1/CXCR4 axis.

The Intricate Role of CXCR4 in Cancer

“…In this study, OS was found to significantly correlate with CXCR4 expression, with the HR of 2.63 (95% CI: 1.69–4.09; P <0.0001), and a significant association was also detected between CXCR4 expression and tumor stage (odd ratio (OR): 0.52, 95% CI: 0.32–0.83; P = 0.007), depth of invasion (OR: 0.44, 95% CI: 0.27–0.73; P = 0.001), lymph node metastasis (OR: 2.30, 95% CI: 1.57–3.36; P <0.0001), and vascular invasion (OR: 0.72, 95% CI: 0.53–0.98; P = 0.04) (Han et al, 2014). Fakhari et al (2014) reported that Helicobacter pylori infection increased CXCL12 secretion by gastric epithelial cell line, upregulated CXCR4 expression in bone marrow-derived-mesenchymal stem cells, and enhanced their migration toward CXCL12 gradient. Findings by Oh et al (2012) indicate that hypoxia upregulates CXCR4 in gastric cancer cells in a HIF-1α-dependent manner and that upregulation of CXCR4 is involved in gastric cancer cell migration and invasion.…”

Mesenchymal Stem Cells in Gastric Cancer: Vicious but Hopeful

“…In most circumstances, the active recruitment of MSC commonly occurs ahead of GC initiation, especially in Hp-related carcinogenesis. Hp induced inflammation milieu is abundant in functional molecules such as TNF-a, TGF-b, CXCL12 and interferon g that conducive to MSC recruitment for their tissue healing functions (28,(87)(88)(89). Corresponding to this point, Ruan et al (27) labeled MSC with amino-modified FMNP that keep stable fluorescent signal and magnetic properties with 14 days to display out the early gastric cancer (EGC) area, not only being with the potential of imaging EGC, these MSC also could inhibit tumor growth markedly under alternating magnetic field irradiation.…”

“…In most circumstances, the active recruitment of MSC commonly occurs ahead of GC initiation, especially in Hp-related carcinogenesis. Hp induced inflammation milieu is abundant in functional molecules such as TNF-α, TGF-β, CXCL12 and interferon γ that conducive to MSC recruitment for their tissue healing functions ( 28 , 87 – 89 ). Corresponding to this point, Ruan et al.…”

Human Bone Marrow Mesenchymal Stromal Cells Attenuate Tissue Injury and Reduce Inflammation in Experimental Acute Pancreatitis

“…In order to prepare hBM-MSCs, bone marrow aspirate was harvested from the iliac crest of a normal donor who was negative for HIV, HBV and HCV laboratory tests, after informed consent was obtained. Then, hBM-MSCs were cultured and isolated as previously reported 26 . Mononuclear cells (MNC) were isolated by gradient centrifugation at 2,500 rpm for 30 minutes on Ficoll-Paque™ Plus (Amersham Pharmacia Biotech, Uppsala, Sweden).…”