All the experiments were performed according to approved protocol by Northeast Ohio Medical University, IACUC. Mouse Lewis lung carcinoma (LLC) cells (2 × 106) were subcutaneously injected in the flank region of wild type C57BL/6 mice (WT) or TRPV4 knockout mice in C57BL/6 background (KO). Tumor size was measured using calipers at 7, 14 and 21 days and tumor volume was calculated according to the formula V= 4/3*Pi*Length/2*(width/2)2. At day 21, mice were euthanized and tumor tissues were collected and fixed for immunohistochemistry or stored at -80°C. To measure tumor angiogenesis, tumor tissue sections of 10 μm thicknesses were stained with anti-CD31 (PECAM-1) to visualize the microvessels, α-SMA to stain pericytes and DAPI to label the nuclei. Images were acquired using Olympus IX72 microscope and the microvessels density, diameter (Feret) and length were calculated using Image J software. For the in vivo drug experiments, six to eight mice/group were used and the animals were divided in to four groups: 1) WT (control) 2) WT + TRPV4 activator 3) WT + Cisplatin and 4) WT + TRPV4 activator + Cisplatin. Once the tumors were palpable (after 7 days), the mice were daily given an intraperitonial (i.p) injection of TRPV4 agonist GSK1016790A (10 μg/kg) to groups 2 and 4 until day 21. The anti-cancer drug Cisplatin (3 mg/kg/week) was administered i.p. once/week to groups 3, and 4, 3 days post treatment with TRPV4 activator, until day 21. The WT control received saline as a vehicle.