MP-02.07 Calcium Depending Bone Metastases in Renal Cell Carcinoma

Migration of renal tumor cells depends on dephosphorylation of Shc by PTEN.

The tumor suppressor PTEN is a phosphatase using FAK and Shc as direct substrates, and Akt as a key effector via PIP3. PTEN regulates cell migration and may influence metastases. We quantified PTEN in 135 clear cell renal cell carcinomas (ccRCC) by Western blot analysis and found statistically significant lower PTEN expression in patients who died, usually caused by metastases, within 5 years after surgery, compared to those surviving this time period. In athymic mice, PTEN transfected 786-O cells were injected into the tail vein and metastatic load of the lungs was quantified. We observed a strongly reduced metastatic load after PTEN transfection. For analyses of the PTEN activities, trans…

Migration of renal carcinoma cells is dependent on protein kinase Cδ via β1 integrin and focal adhesion kinase

Migration and adhesion of tumor cells are essential prerequisites for the formation of metastases in malignant diseases. Protein kinase C (PKC) has been shown to regulate cell migration, adhesion and proliferation. In order to identify a connection between PKC isoforms and tumor progression in renal cell carcinoma (RCC), the influence of PKC isoforms on cell migration, adhesion and proliferation and possible influences of the activity of integrins and focal adhesion kinase (FAK) were analyzed in RCC cells. The experiments were performed in the RCC cell line CCF-RC1 after pre-incubation of the cells with the PKC inhibitors GF109203X, GO6976, RO31-8220 and rottlerin. Cell migration and adhesi…