Modeling of Invadopodia Mediated Extracellular Matrix Degradation

Breast cancer is the most common type of cancer found in female patients worldwide. Generally breast cancer mortality is not a result of primary tumor formation, but the result of the metastatic disease. Tumor metastasis is the process by which cancer cells spread from a primary tumor site and re-establish themselves in a secondary location. One hypothesis for how tumor cells can spread is through the upregulation of invadopodia. Invadopodia are actin-rich organelles which play a role in the remodeling and degradation of the extracellular matrix (ECM), which is required for tumor cell invasion. These organelles are often seen in invasive cancer cell lines in vitro. Invadopodia is able to mediate degradation of the ECM by several types of metalloproteases being at its location. One protease that is essential to invadopodia is the Membrane Type 1-Metalloprotease (MT1-MMP). Though MT1-MMP plays a key role in invadopodia proteolytic activity, the molecular components which regulate invadopodia assembly and metalloprotease recruitment are not clearly elucidated. Our goal is to create two fluorescently tagged MT1-MMP lentiviral expression constructs for live cell imaging of invadopodia and invadopodia mediated degradation in various breast cancer cell lines. Overall these experiments will help us further dissect the timing in which various molecular components are required for invadopodia assembly.