Carrington, James; Xue, Qian; Roh-Johnson, Minna (University of Utah)
Faculty Advisor: Roh-Johnson, Minna (University of Utah, Biochemistry)
Metastasis of melanoma to distant sites of the body result in poor patient prognosis with a high mortality rate (76%). Cell migration has been studied in vitro and focal adhesions, which allow cells to move forward by attaching to extracellular matrix (ECM) on the front of the cell and breaking down at the back of the cell, have been shown to play important roles in locomotion. However, it has been difficult to visualize these structures in vivo, especially during tumor cell dissemination. Understanding how cancer cells are utilizing focal adhesions could play an important role in developing therapeutics to counteract metastasis using focal adhesion inhibitors and lead to improved patient outcomes. This research focuses on identifying if a previously observed focal adhesion marker in melanoma is formed at surfaces where cells are in contact with ECM. Because zebrafish share 80% disease homology with humans and are transparent during early embryonic development, they provide an optimal model for visualizing cell migration while still maintaining physiological significance. To identify if migrating melanoma cells are in contact with ECM, we injected fluorescently labeled melanoma cells in zebrafish. We allowed the melanoma cells to migrate and labeled components of the ECM (laminin, collagen, and fibronectin). We then imaged the zebrafish and determined the proximity of melanoma cells to the ECM. We also used transmission electron microscopy to identify the location of melanoma cells in respect to the ECM. We found that melanoma cells are in contact with ECM in vivo. The in vivo contact of focal adhesion markers in melanoma with ECM suggests that focal adhesions can be visualized and studied in zebrafish. Future studies will examine how focal adhesion formation is regulated and how inhibiting their function will impact tumor cell dissemination.