作者
Michela Bernardini, Alessia Brossa, Giorgia Chinigo, Guillaume P Grolez, Giulia Trimaglio, Laurent Allart, Audrey Hulot, Guillemette Marot, Tullio Genova, Aditi Joshi, Virginie Mattot, Gaelle Fromont, Luca Munaron, Benedetta Bussolati, Natalia Prevarskaya, Alessandra Fiorio Pla, Dimitra Gkika
发表日期
2019/7/8
期刊
Cancers
卷号
11
期号
7
页码范围
956
出版商
MDPI
简介
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.
引用总数
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