Gastric Cancer Mesenchymal Stem Cells Trigger Endothelial Cell Functional Changes to Promote Cancer Progression.
Linjing CuiTing LiuChao HuangFumeng YangLiqi LuoLi SunYuanyuan ZhaoDeqiang WangMei WangYong JiWei ZhuPublished in: Stem cell reviews and reports (2024)
Our previous studies have highlighted the pivotal role of gastric cancer mesenchymal stem cells (GCMSCs) in tumor initiation, progression, and metastasis. In parallel, it is well-documented that endothelial cells (ECs) undergo functional alterations in response to challenging tumor microenvironment. This study aims to elucidate whether functional changes in ECs might be induced by GCMSCs and thus influence cancer progression. Cell proliferation was assessed through CCK-8 and colony formation assays, while cell migration and invasion capabilities were evaluated by wound-healing and Transwell assays. Immunohistochemistry was employed to examine protein distribution and expression levels. Additionally, quantitative analysis of protein and mRNA expression was carried out through Western blotting and qRT-PCR respectively, with gene knockdown achieved using siRNA. Our findings revealed that GCMSCs effectively stimulate cell proliferation, migration, and angiogenesis of human umbilical vein endothelial cells (HUVECs), both in vitro and in vivo. GCMSCs promote the migration and invasion of gastric cancer cells by inducing the expression of Slit2 in HUVECs. Notably, the inhibition of phosphorylated AKT partially mitigates the aforementioned effects. In conclusion, GCMSCs may exert regulatory control over Slit2 expression in ECs via the AKT signaling pathway, thereby inducing functional changes in ECs that promote tumor progression.
Keyphrases
- endothelial cells
- cell proliferation
- poor prognosis
- mesenchymal stem cells
- signaling pathway
- binding protein
- pi k akt
- papillary thyroid
- high glucose
- single cell
- vascular endothelial growth factor
- umbilical cord
- cell cycle
- wound healing
- high throughput
- stem cells
- cell therapy
- bone marrow
- squamous cell
- high resolution
- epithelial mesenchymal transition
- south africa
- protein protein
- squamous cell carcinoma
- genome wide
- copy number
- childhood cancer