VCaP Prostate cancer cell line derived xenograft (CDX) model in SRG™ rats & mice
VCaP is a prostate cancer cell line that exhibits many of the characteristics of clinical prostate carcinoma, including expression of PSA, PAP, and AR. VCaP cells also express retinoblastoma (Rb) and p53 (with a A248W mutation). Take rates and growth kinetics for the VCaP line are dismal in mouse models. However, Hera has demonstrated efficient engraftment (60%) with favorable growth kinetics in the Rag2/Il2rg double knockout SCID, SRG™ rat model on a Sprague-Dawley background strain.
VCaP cell line derived xenograft (CDX) in SRG rats- pilot study
5 male SRG rats each received 10M VCaP cells on either side of the flank. Body weights and tumor volume measurements were taken three times a week. Weekly blood collection and serum separation to measure PSA indicates that the PSA levels correlate to tumor growth.
Although tumor take rates and growth kinetics in mouse models are not ideal for VCaP, studies have been performed demonstrating the utility of VCaP for in vivo studies. The investigators in Therapeutic Targeting of BET Bromodomain Proteins in Castration-Resistant Prostate Cancer, (Asangani et al. Nature 2014) used VCaP in SCID mice to demonstrate superior efficacy of BET bromodomain inhibition (JQ1) compared to direct AR antagonism (MDV3100). Male SCID C.B17 mice of four weeks in age were implanted subcutaneously with 2×106 VCaP prostate cancer cells suspended in PBS with 50% Matrigel into each side of the dorsal flank. Animals were randomized once the tumors reached palpable stage (100mm3) and treated, five days a week for 6 weeks. Tumor growth was recorded and tumor volumes were calculated. A significant decrease in tumor volume/weight was observed in VCaP tumor-bearing SCID mice treated with JQ1; whereas MDV3100 was less efficacious as demonstrated in the figure below (from Asangani et al. Nature 2014).
BET bromodomain inhibition blocks prostate cancer in vivo, using VCaP as a model
VCaP cells were implanted subcutaneously in mice and grown until tumors reached the size of approximately 100mm3. Xenografted mice were randomized and then received (n=6 per group) vehicle, 50mg/kg JQ1 or 10mg/kg MDV3100 as indicated 5days/week (Asangani et al.).