STUDY OF MOLECULAR DYNAMICS IN LEUKOCYTE-ASSISTED MELANOMA EXTRAVASATION

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cancer is the second leading cause of death in the United States. The ability of cancer to metastasize is one reason why cancer is so deadly and treatment difficult. If the cancer can be contained to one tumor, the survival rate is much greater than in patients with cancer that has metastasized. Successful metatasis requires a series of complex steps. These steps can be summarized into four main steps: 1) invasion, 2) transport, 3) adhesion and 4) extravasation. Inhibition of any of the steps in the metastatic cascade will prevent or slow metastasis. This protocol will study the adhesion and extravasation steps by which melanoma migration occurs. The adhesion process occurs by a cascade of molecular interactions between the endothelium and the adhering cell. Adhesion molecules such as selectins and integrins modulate this process. Because the endothelium and melanoma cells both express relatively high levels of ICAM-1 and not ICAM-1's corresponding ligands MAC-1 and LFA-1, a bridge, in this case a leukocyte, is helpful in achieving efficient adhesion between the two cells. Leukocytes have been shown to express relatively high values of LFA-1, an ICAM-1 ligand. Using flow cytometry to quantify and characterize the adhesion molecules on melanoma, human leukocytes and endothelial cells and an in vitro flow migration assay to measure migration and extravasation, the investigators can examine factors that contribute to or hinder the metastasis cascade.