P. Brodt

Biography

We are studying molecular aspects of cancer metastasis. In this context, the roles of cell adhesion receptors, cytokines and growth factors in the regulation of angiogenesis, cancer cell invasion and metastasis are being investigated. The following projects are in progress. A. The role of the type 1 Insulin-like growth factor receptor (IGF-1R) in metastasis. We identified the IGF-I receptor as a regulator of tumor cell invasion and metastasis. Receptor domains with distinct contributions to the metastatic phenotype were identified. Presently, we are investigating signal transduction pathways involved in transcriptional regulation by IGF-IR, using a combination of approaches that include gene transfer, use of dominant negative mutants and promoter assays. The contribution of different receptor domains to transcriptional regulation of different genes is also being investigated. In parallel, the role of post internalization, receptor-ligand complex processing in signaling is being investigated. B. Gene therapy of cancer metastases. Multiple strategies are being developed for gene therapy of metastases based on targeting and disruption of IGF-IR synthesis and/or signaling. These strategies are being tested in several cancer types including colorectal carcinoma, breast carcinoma and brain tumors. C. Tumor-endothelial cell interactions: role in liver metastasis. We have shown that the endothelial cell adhesion receptor E-selectin mediates carcinoma cell adhesion to liver sinusoidal endothelial cells and liver metastasis (Khatib et al, Cancer Res. 62:2002). Presently, the molecular cascade that is initiated following tumor cell entry into the hepatic circulation is being investigated by a combination of in vivo and in vitro techniques. In particular, the roles of E-selectin, VCAM-1, PECAM-1 and ICAM-1 and of inflammatory cytokines and chemokines are being analysed. A combination of immunohistochemistry, fluorescence based techniques and molecular analyses if being used.

Research Interest

Molecular Basis of Cancer Metastasis - Identification of molecular targets for anti-cancer therapy.