Abstract

Abstract Although genetic mouse models for cancer and human tumor cell xenotransplantation models in rodents remain essential, such systems are costly, slow, and not amenable to high-throughput assays for cancer drug target discovery. There is a clear need to develop fast, semi-automated in vivo systems for medium to high-throughput screening applications in preclinical target discovery and lead compound identification. In this study, we developed an automated, semi-high throughput, noninvasive and quantitative platform for imaging one critical aspect of cancer progression, namely tumor cell dissemination, in a zebrafish xenotransplantation model. This is the first semi-automated whole organism based bio-imaging assay of tumor progression in a vertebrate. We have used this platform to screen for prostate cancer relevant drug and gene targets, and have identified novel regulators of prostate cancer dissemination. Using 3D in vitro invasion assays, we show a critical role for these molecules in prostate cancer migration strategies. Further validation of these targets is underway in mouse models and human cancer specimens. Citation Format: Veerander Paul Singh Ghotra, Shuning H.E., Hans De Bont, H.P. Spaink, Bob Van de Water, B. Ewa Snaar Jagalska, Erik H.J. Danen. Semi-high-throughput whole-animal bioimaging assay identifies novel players in prostate cancer progression [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr C52.

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