Activation of mechanosensitive ion channel TRPV4 normalizes tumor vasculature and improves cancer therapy.

ABSTRACT: Tumor vessels are characterized by abnormal morphology and hyperpermeability that together cause inefficient delivery of chemotherapeutic agents. Although vascular endothelial growth factor has been established as a critical regulator of tumor angiogenesis, the role of mechanical signaling in the regulation of tumor vasculature or tumor endothelial cell (TEC) function is not known. Here we show that the mechanosensitive ion channel transient receptor potential vanilloid 4 (TRPV4) regulates tumor angiogenesis and tumor vessel maturation via modulation of TEC mechanosensitivity. We found that TECs exhibit reduced TRPV4 expression and function, which is correlated with aberrant mechanosensitivity towards extracellular matrix stiffness, increased migration and abnormal angiogenesis by TEC. Fur

SUBMITTER: Adapala RK 

PROVIDER: S-EPMC4948740 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature