Unlocking the mechanism of kallikreins modulating the adhesion of prostate cancer cells to bone

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Members of the kallikrein family of serine proteases are strongly associated with prostate cancer. Preliminary experiments with prostate cancer cells expressing the kallikreins hK3 and hK4 suggest that hK3 and hK4 lead to EMT-like changes (EMT: epithelial to mesenchymal transformation) in these cells. Hence, it may be supposed that hK3 and hK4 are involved in the progression of localized prostate cancer to a metastatic stage. Since the development of prostate cancer metastases, mainly located in bone, results in poor prognosis for patients, it is of great importance to study the mechanisms that enable prostate tumor cells to adhere to the bone environment. To investigate if decreased E-cadherin levels upon hK3 and hK4 expression lead to decreased cell-cell adhesion, functional cell adhesion assays are needed. For that purpose single-cell force spectroscopy, an atomic force microscopy based approach, may be used. Besides cell-cell adhesion, adhesion of PC3 cells to matrices that mimic the bone ECM may be analyzed. These experiments will help to understand the molecular mechanisms by which tumor cells interact with the bone environment during the development of bone metastases. Complementary to the adhesion measurements, the link between kallikreins and adhesion molecule expression will be investigated using cell biological and biochemical analysis techniques.