Research / Clinical Summary

James Quigley, PhD Professor, Cell Biology, Scripps Research Institute Contact by Email

My research involves the establishment and analysis of model systems that recapitulate cancer invasion, metastasis and angiogenesis. We are conducting studies on the mechanism of human tumor metastasis using an in vivo model system that employs human tumor cells disseminating to specific organs in the chick embryo. A technique known as subtractive immunization is employed to generate unique antibodies directed against antigens on the surface of metastatic human tumor cells. Highly selected panels of monoclonal antibodies have been tested for their ability to modulate metastatic spread. Tumor cell surface antigens that are functionally involved in metastasis are being molecularly cloned, identified and characterized by these methods.

The laboratory has also recently begun a full scale investigation of the least-studied step in metastasis, namely intravasation, the entry of primary tumor cells into the vasculature which is a prerequisite for cancer cells to disseminate. Thus intravasation is likely a rate-limiting step in metastasis and the identification of contributory molecules is a goal of the lab.

My laboratory is also examining the differential expression of specific proteolytic enzymes and how they may mediate angiogenesis and tumor cell migration and invasion. The experimental approach is to employ highly sensitive assays to detect those enzymes which are elevated in angiogenic tissue, or in invading tumor cells, to purify the enzymes, design inhibitory RNAs (RNAi) against them and raise neutralizing antibodies to the enzymes. Then we test the purified enzymes, the isolated antibodies, and the expressed RNAi in various model systems that mimic the angiogenic or invasive phenotype. This approach allows for the identification of specific molecules that are functionally involved in distinct biological processes. Two enzyme systems presently under study include the matrix metallo proteases (collagenases and gelatinases) and a new family of cell membrane-anchored serine proteases.

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