Predictive Markers of Tumor Micrometastasis
Fig. 1: E-cadherin loss and p120 overexpression in a case of clear renal cell carcinoma (cRCC). Normal tissue is shown in the top and tumor in the bottom panels.
E-cadherin loss and p120 overexpression in a case of clear renal cell carcinoma
The epithelial model systems we currently use in the lab involve breast, renal and lung cancer. More specifically, in the case of renal (kidney) cancer we have preliminary evidence that E-cadherin downregulation and HGF/c-Met signaling are important pathways mediating tumor cell invasiveness. We are currently testing the involvement of the cadherin/catenin system in renal cancer micrometastasis, which is the major cause of death in patients that were initially diagnosed with early stage disease. Our goal is to validate p120 and other metastasis related proteins as valuable targets for the development of novel therapeutics, as well as to determine whether the expression of a panel of metastasis-related proteins can predict which patients are more likely to develop metastasis following the initial tumor excision (nephrectomy). These patients could then be followed up more closely, or receive more aggressive treatments to improve their outcome.
Similarly, in the case of breast cancer, we are very interested in identifying molecular pathways that promote metastasis to particular sites, especially to bone and brain. One of the hypotheses we are testing is that inappropriate expression of mesenchymal cadherins by breast cancer cells promotes metastasis to bone or brain depending on the cadherin expressed.