Transient Receptor Potential Channel Expression Signatures in Tumor-Derived Endothelial Cells: Functional Roles in Prostate Cancer Angiogenesis

肿瘤来源的内皮细胞中的瞬时受体电位通道表达特征:在前列腺癌血管生成中的功能作用

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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 Gkika0

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.

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.

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.

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