Basement Membrane Collagens and Cancer

The development of cancer is a complex multistage event that requires tumor cell growth, adhesion, migration, and invasion. Tumor growth is strictly dependent on angiogenesis, the formation of new blood vessels from preexisting vasculature, which involves endothelial cell proliferation, migration, and tubulogenesis. The steps involved in angiogenesis and tumor cell dissemination include the destruction of basement membranes (BM), specialized extracellular matrix structures that separate epithelia from the surrounding stroma. Collagens represent the major component of all basement membranes. In addition to providing mechanical stability and scaffold for the assembly of other molecules, collagens also directly affect multiple aspects of cell behavior. In the last decades, our understanding of the events involved in tumor progression has increased considerably because of the discovery of a number of collagen cleavage products that strongly affect the behavior of tumor and endothelial cells, and the recognition that endothelial and tumor cells play an active role in the production and degradation of ECM components. In this chapter, we focus on the structure and role of BM collagen molecules in the control of tumor-associated angiogenesis and tumor progression. We describe: (1) the composition of the major types of collagen in basement membranes; (2) the interaction of these components with tumor and endothelial cells; (3) the role of intact collagen molecules and their cleavage products in the control of specific steps of tumor progression (migration, invasion, and recruitment of blood vessels); and (4) how collagen-derived fragments may potentially be used as therapeutic tools for the treatment of cancer.