Bone marrow‐derived mesenchymal stem cells promote Helicobacter pylori ‐associated gastric cancer progression by secreting thrombospondin‐2
| Autor: | Chen Jiang, Cuihua Qi, Mengke Fan, Qin Zhang, Lingjun Meng, Hailing Yao, Xiaohua Hou, Huiying Shi, Rong Lin |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Male
Bone Marrow Cells Immunofluorescence Helicobacter Infections Mice Bone Marrow Stomach Neoplasms medicine Animals Humans Helicobacter Gastric cancer (GC) Cell Proliferation Mice Inbred BALB C Helicobacter pylori biology medicine.diagnostic_test business.industry Stomach Mesenchymal stem cell Bone marrow‐derived mesenchymal stem cells (BM‐MSCs) Cancer Cell Differentiation Epithelial Cells Mesenchymal Stem Cells Original Articles Cell Biology General Medicine biology.organism_classification medicine.disease Cancer‐associated fibroblasts (CAFs) medicine.anatomical_structure Gastric Mucosa Cancer research Original Article Female Bone marrow Thrombospondins business Thrombospondin‐2 Fluorescence in situ hybridization |
| Zdroj: | Cell Proliferation |
| ISSN: | 1365-2184 0960-7722 |
| Popis: | 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. Bone marrow mesenchymal stem cells transplanted in mice with chronic H pylori infection gradually migrate from the subserosa to the mucosa and secret THBS2 protein to promote the occurrence and development of gastric cancer. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text