Abstract
Background: 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.
Highlights
IntroductionTransient receptor potential (TRP) channels form a 28-member superfamily of nonselective channels mostly permeable to both monovalent and divalent cations, which is subgrouped into six main families, namely, TRPC (canonical), TRPV (vanilloid), TRPM (melastatin), TRPP (polycystin), TRPML (mucolipin), and TRPA (ankyrin)
Transient receptor potential (TRP) channels form a 28-member superfamily of nonselective channels mostly permeable to both monovalent and divalent cations, which is subgrouped into six main families, namely, TRPC, TRPV, TRPM, TRPP, TRPML, and TRPA
The results described above indicate that TRPA1 is a modulator of Prostate tumor ECs (PTEC) migration, raising the this point, we tested TRPA1 and other TRP candidates for their ability to organize into capillary-like question of whether this channel affects tubulogenesis or in vivo angiogenesis
Summary
Transient receptor potential (TRP) channels form a 28-member superfamily of nonselective channels mostly permeable to both monovalent and divalent cations, which is subgrouped into six main families, namely, TRPC (canonical), TRPV (vanilloid), TRPM (melastatin), TRPP (polycystin), TRPML (mucolipin), and TRPA (ankyrin). Cancers 2019, 11, 956 polymodal molecular sensors and are activated by a range of external stimuli (including temperature, light, sound, chemicals, and touch) and changes in local microenvironment [1] These observations suggest that the physiologically relevant stimulus for any given TRP is governed by the specific cellular context, which dramatically changes during carcinogenesis [2]. 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. 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
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