Angiogenesis is essential for the growth of primary and metastatic tumors. It has recently been demonstrated that senescent human fibroblasts secrete increased amounts of vascular endothelial growth factor (VEGF), which could, at least in part, underlie the tumor-promoting effect of senescent fibroblasts in vivo. Since it is believed that reciprocal interactions between peritoneal mesothelial cells and ovarian cancer cells may be crucial for the intraperitoneal invasiveness of the cancer, we analyzed the production of pro-angiogenic growth factors (VEGF) and chemokines (CXCL1, CXCL8 and CCL2) by human peritoneal mesothelial cells (HPMCs).
Experiments were conducted using an in vitro model, in which primary omentum-derived HPMCs were forced to senescence by serial passaging. Levels of the pro-angiogenic agents in cell culture supernatants were quantified using specific ELISA-based assays. In addition, the MTT test was performed to assess proliferation of endothelial cells (EAhy926 line) exposed to conditioned medium (CM) from the consecutive passages of HPMCs. The results are expressed as means+/-SEMs, and analyzed by the paired t-test.
The studies showed that senescent HPMCs are characterized by the increased secretion of VEGF (786+/-222 vs. 149+/-42 pg/10(5) cells, p
These results indicate that senescent HPMCs produce increased levels of pro-angiogenic mediators that by stimulating endothelial cell growth may promote tumour neovascularisation.