Abstract A15: High-Content screen for inhibitors of cell migration in cancer metastasis using adenoviral knock-down

Enhanced cell migration is a hallmark of metastatic cancer cells. The propensity of cancer cells to close an open wound in a cell monolayer is thought to predict this ability. Using our adenoviral shRNA knockdown library we have established a high-throughput wound healing assay to identify novel genes involved in cell migration. A 96-pin tool was designed to apply a constant mechanical scratch-wound in the cellular monolayer. We used transmitted light imaging for segmentation and quantification of the scratch wound that remained open. Genes whose knockdown inhibit cell migration can be identified by their effect on the open wound. We demonstrated that two knockdown constructs targeting a known player in motility, CXCR4, inhibit wound healing, thereby validating our approach. Using this wound healing assay we have identified a number of novel genes associated with cancer cell motility. These targets have consecutively been validated for their role in 3-D invasion using Boyden chambers. As our adenoviral knockdown libraries focus on druggable targets, these validated targets can quickly be employed to generate small-molecule compounds or antibody therapeutics targeting cancer metastasis. Citation Format: Remko de Pril, Annemarie Lekkerkerker, Desire van Steenhoven, Ilhem Maghrani, Tim Perera, Janine Arts, David Fischer, Richard Janssen. High-Content screen for inhibitors of cell migration in cancer metastasis using adenoviral knock-down [abstract]. In: Proceedings of the AACR Special Conference on Chemical Systems Biology: Assembling and Interrogating Computational Models of the Cancer Cell by Chemical Perturbations; 2012 Jun 27-30; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2012;72(13 Suppl):Abstract nr A15.