Transient receptor potential (TRP) channels control multiple processes involved in cancer progression by modulating cell proliferation, survival, invasion and intravasation, as well as, endothelial cell (EC) biology and tumor angiogenesis. Nonetheless, a complete TRP expression signature in tumor vessels, including in prostate cancer (PCa), is still lacking. Methods: In the present study, we profiled by qPCR the expression of all TRP channels in human prostate tumor-derived ECs (TECs) in comparison with TECs from breast and renal tumors. We further functionally characterized the role of the ‘prostate-associated’ channels in proliferation, sprout formation and elongation, directed motility guiding, as well as in vitro and in vivo morphogenesis and angiogenesis. Results: We identified three ‘prostate-associated’ genes whose expression is upregulated in prostate TECs: TRPV2 as a positive modulator of TEC proliferation, TRPC3 as an endothelial PCa cell attraction factor and TRPA1 as a critical TEC angiogenic factor in vitro and in vivo. Conclusions: We provide here the full TRP signature of PCa vascularization among which three play a profound effect on EC biology. These results contribute to explain the aggressive phenotype previously observed in PTEC and provide new putative therapeutic targets.
(B) Chemotaxis chambers were used to study hTERT PTEC-directed migration in the presence of hTERT PTEC-, TRPC3-overexpressing HMEC-, HMEC- or non-conditioned (non-cond) media. Compared to HMEC conditioned medium, PTEC conditioned medium (24-h conditioning) increased PC3 cell speed (c, left panel), while compared to control HMEC conditioned medium, the conditioned medium from TRPC3-overexpressing HMECs significantly promoted PC3 migration via directional persistence index and not on the speed (c, central and right panels).
In this study, µ-Slide Chemotaxis, was used to determine the speed and directionality of the PC3 migration cells in the preescence of immortalized PTEC (hTERT PTEC)-, TRPC3-overexpressing HMEC-, HMEC- or non-conditioned (non-cond) media.
Credit: Bernardini et al.