Targeting fibroblast activation protein inhibits endothelial-mesenchymal transition by affecting cancer-associated fibroblasts derived exosomes北大核心CSCD

Aim To investigate whether targeted inhibition of fibroblast activation protein (FAP) can inhibit the endothelial-to-mesenchymal transition (EndMT) of vascular endothelial cells by affecting exosomes (Exo) of cancer-associated fibroblasts (CAFs) and explore the underlying mechanisms. Methods Primary CAFs and peri-tumor fibroblasts (PTFs) were obtained from lung cancer and peri-cancer tissues, and CAFs-exo and PTFs-exo were collected from culture medium, respectively. Exosomes from CAFs treated with specific FAP inhibitor (3.3 nmol • L-1 SP13786) for 24 h were named as Anti-FAP-exo. HMEC-1 cells were incubated in equal volumes of RPMI 1640, PTFs-exo, CAFs-exo and anti-FAP-exo respectively and named as control group, PTF group, C AF group and anti-FAP group. The scratch assay, Transwell invasion assay and angiogenesis assay were used to detect the migration ability, invasion ability and angiogenesis ability of HMEC-1 cells. Immunofluorescence, immunohistochemistry and Western blot were used to detect EndMT-associated protein expression. Results The migration ability, invasion ability and angiogenesis ability of HMEC-1 cells of CAF group were significantly higher than those of PTF group, whereas there was no significant difference between that of anti-FAP group and PTF group. HMEC-1 cells of CAF group had higher expression of α-SMA, SM22α, p-Stat3 and Snail, and lower expression of CD31 and VE-cadherin than that of PTF group. In addition, HMEC-1 cells of Anti-FAP group had lower expression of α-SMA, SM22α, pStat3 and Snail, and higher expression of CD31 and VE-cadherin than that of CAF group. Conclusions Specific inhibition of FAP could indirectly inhibit the migration ability, invasion ability and angiogenesis ability of vascular endothelial cells via affecting CAFs-exo and Stat3-snail-EndMT pathway may be the potential mechanism. © 2023 Publication Centre of Anhui Medical University. All rights reserved.