Control of Prostate Cancer Cell Growth and Survival by the Extracellular Matrix

The scope of this grant proposal is to investigate whether adhesion of prostate cancer cells to extracellular matrices regulates cell growth and survival. We have shown that attachment of LNCaP cells to a variety of matrices results in the phosphorylation of the focal adhesion kinase(FAK) and the scaffolding protein, p130. Downstream effectors of this signalling pathway in LNCaP cells include the Crk family of proteins, and the Crk binding proteins, C3G and DOCK180. Therefore upon adhesion of LNCaP cells, signalling pathways to the nucleus and cytoskeleton become activated to cause cell proliferation and cytoskeletal reorganization. We have set up a proliferation assay and measured a 15 - 20% increase in cell proliferation upon adhesion of LNCaP cells to fibronectin, collagen I and matrices generated by cultured osteoblastic cells. In addition, adhesion also prolonged the survival of LNCaP cells. Our results demonstrate, that adhesion to the substratum plays an important role in the regulation of proliferation and survival of LNCaP cells.