Bone marrow‐derived mesenchymal stem cells promote Helicobacter pylori‐associated gastric cancer progression by secreting thrombospondin‐2

Abstract

Objectives Bone marrow‐derived cells (BMDCs), especially mesenchymal stem cells (MSCs), may be involved in the development of Helicobacter pylori‐associated gastric cancer (GC) in mice, but the specific mechanism remains unclear, and evidence from human studies is lacking. Materials and Methods To verify the role of BM‐MSCs in H pylori‐associated GC, green fluorescent protein (GFP)‐labelled BM‐MSCs were transplanted into the subserosal layers of the stomach in a mouse model of chronic H pylori infection. Three months post‐transplantation, the mice were sacrificed, and the gastric tissues were subjected to histopathological and immunofluorescence analyses. In addition, we performed fluorescence in situ hybridization (FISH) and immunofluorescence analyses of gastric tissue from a female patient with H pylori infection and a history of acute myeloid leukaemia who received a BM transplant from a male donor. Results In mice with chronic H pylori infection, GFP‐labelled BM‐MSCs migrated from the serous layer to the mucosal layer and promoted GC progression. The BM‐MSCs differentiated into pan‐cytokeratin‐positive epithelial cells and α‐smooth muscle actin‐positive cancer‐associated fibroblasts (CAFs) by secreting the protein thrombospondin‐2. FISH analysis of gastric tissue from the female patient revealed Y‐chromosome‐positive cells. Immunofluorescence analyses further confirmed that Y‐chromosome‐positive cells showed positive BM‐MSCs marker. These results suggested that allogeneic BMDCs, including BM‐MSCs, can migrate to the stomach under chronic H pylori infection. Conclusions Taken together, these findings imply that BM‐MSCs participate in the development of chronic H pylori‐associated GC by differentiating into both gastric epithelial cells and CAFs.

Diagnostic and Prognostic Roles of Thrombospondin-2 in Digestive System Cancers

“…And in gastric cancer, OS rates were higher in the high TSP-2 group [ 29 ]. The reason may be that TSP-2 can promote the progression of Helicobacter pylori-associated gastric cancer [ 30 ].…”

Helicobacter Pylori and Its Role in Gastric Cancer

“…HB-EGF also contributes to GC progression by potentiating the epithelial-mesenchymal transition [162]. H. pylori infection also affects mesenchymal stem cells (MSCs) by inducing their migration to the gastric mucosa, where they may contribute to GC development by differentiating into epithelial cells or assisting in angiogenesis [163]. HpGGT was recently shown to disturb MSCs by obstructing alpha-ketoglutarate to boost trimethylation of histones H3K9 and H3K27, triggering PI3K/AKT signaling, and helping proliferation, migration, self-renewal, and pluripotency in cancerogenesis [164].…”

Effects of helicobacter pylori on tumor microenvironment and immunotherapy responses

“…Overexpressed THBS4 then mediates BM-MSC-induced angiogenesis in GC by activating the THBS4/integrin α2/PI3K/AKT pathway ( 45 ). Moreover, BM-MSCs can differentiate into pan-cytokeratin-positive (pan-CK + ) epithelial cells and alpha-smooth muscle actin (α-SMA + ) cancer-associated fibroblasts (CAFs) by secreting THBS2, thus promoting the development of H. pylori -associated GC ( 46 ).…”