In Vitro Matrices for Studying Tumor Cell Invasion

Metastasis is the major cause of death in patients with cancer and thus attempts have been made for more than a century to experimentally dissect its component parts. Multiple arbitrary divisions have been offered that often begin with immortalized and transformed cells demonstrating altered cell proliferation, cell cycle and apoptotic pathways initiating their journey of dissemination by detaching from the primary tumor mass, initiating angiogenesis, degrading and penetrating the basement membranes and the surrounding connective tissue boundaries, intravasating, circulating and extravasating through the blood or lymphatic circulation and after evading the immune system eventually reaching one or more distant metastatic sites where they must undergo a similar process in reverse order. Tumor cell invasion is one of the key steps in this complex process. As the metastatic potential of tumor cells is largely dependent on their ability to degrade and migrate through extracellular matrix (ECM) barriers, inhibition of its subroutines (proteolysis, ECM degradation, chemotaxis, haptotaxis etc.) become logical targets for experimental cancer therapy. To explore potential approaches to inhibit tumor invasion, various in vitro invasion assays have been devised and become widely-accepted surrogate endpoints to mimic the in vivo condition. Most invasion assay systems are based on measuring the ability of cells to invade across purified ECM components such as collagen or complex artificial or reconstituted ECMs. Each has certain strengths, quantitative abilities, ease of manipulation of treatments etc. and like the tumor cells themselves, each is counterbalanced by inherent weaknesses. These are reviewed in this chapter.