Abstract
Abstract VLA-2 is the alpha2beta1 integrin which mediates interactions of cells with collagens, laminin and other extracellular matrix components. In tumor cells, VLA-2 has been described to be involved in neovascularization, tumor-stroma interactions and metastasis. The objective of this study was to assess the potential of VLA-2 as a target in a range of tumor models. We used GBR 500, a monoclonal IgG4 antibody directed against the alpha2 subunit of the alpha2beta1 integrin heterodimer. The antibody binds to human but not to mouse VLA-2. GBR 500 is currently undergoing clinical phase I studies. We first characterized the expression of VLA-2 in a set of 96 commonly used human cancer cell-lines from different tissues/organs (including colorectal, skin, breast, prostate, pancreas, lung, cervix, kidney, ovary, CNS, bone, liver, thyroid, and blood) and screened for growth inhibition in solid tumor subcutaneous xenografts. In an orthotopic mouse xenograft model using a DU145-luc cell line we explored the importance of VLA-2 for tumor growth in a physiological setting. We finally assessed the effect of VLA-2 antagonism on metastasis in a PC-3 luc metastasis model. Results: VLA-2 inhibition leads to modest growth reduction in subcutaneous xenografts. In the orthotopic xenograft stronger tumor growth inhibition was achived. The strongest tumor growth inhibition effects were achieved in the mestastasis model. Conclusion: According to our finding growth inhibition of tumors by VLA-2 inhibition increases with increased stroma exposition Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr C64.
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