We have identified a high molecular weight complex (M-complex) in adult bovine serum that appears to be required for the process for invasion by melanoma and breast cancer cells. The M-complex was purified by immunoaffinity chromatography and found to contain two major components: a 90-kDa (p90) protein and a 22-kDa (p22) protein. Preliminary results show that this complex associates with EDTA-resistant and metallo-type proteases and is capable of inducing cell invasion and binding to the cell surface invadopodia. Binding to invadopodia may result in a cascade of proteolytic events and an increase in extracellular matrix (ECM) degradation.. The goals of this training proposal are to characterize the complex in sera of breast cancer patients and study the nature of its association with breast cancer cells. Ultimately, we hope to examine ECM degradation as a key mechanism controlling breast cancer invasion and to investigate potential application of enzymes such as serum proteases or M- complex as therapeutic targets for metastasis. We postulate that this complex may serve as a vehicle to recruit proteases to cell surface invadopodia, thus promoting breast cancer invasion and metastasis. Identification of cancer activated M-complex will shed light on regulatory mechanisms of metastasis. Thus this proposed investigation may result in the development of a novel therapeutic target for breast cancer.
