In Australia, colorectal cancer (CRC) has the second highest prevalence and mortality of all cancers. CRC has the potential to invade and metastasize if undetected, creating a range of complications. Metastasis causes a dramatic drop in patient survival, however further research is required to understand the underlying mechanisms.
Metastasis is a complex process where cancerous cells invade surrounding tissue, traverse the systemic circulation and deposit in distant locations. Many patients present with symptoms relating to the primary tumour which can be managed with therapies including surgery, radiation and chemotherapy. However, numerous patients develop a metastatic lesion at a secondary site. The process of invasion and migration is commonly thought to involve increased cellular motility, accompanied by proteolytic processing of the extracellular matrix (ECM) allowing subsequent penetration through the surrounding tissues.
Dynamic actin-rich structures known as invadopodia have been identified in several types of tumour cells which possess highly invasive or metastatic potential. Invadopodia adhere to and degrade ECM substrates via the targeted secretion of extracellular proteases and the actions of numerous transmembrane proteases. It is possible that invadopodia play a potential role within colorectal cancer tumour cell invasion.
Using datasets from the Oncomine database, we systematically compared the expression levels of a number of invadopodia-related proteins in CRC. Overexpression of Tks5 and cortactin was observed in tumour tissue compared to normal tissue; and in metastatic versus primary tumours. Our laboratory investigations revealed that invadopodia are present in colon cancer cells and that overexpression of Tks5 or cortactin leads to increased secretion of MMP-2 and invadopodia activity. We also determined that the pro-inflammatory cytokine, IL-6, which has been linked to the advanced stage and decreased survival of CRC patients, also enhances invadopodia in colon cancer cells. Interestingly, we observed that the clinical agent cetuximab increased invadopodia activity in colon cancer cells.