STUDY OF MOLECULAR DYNAMICS IN LEUKOCYTE-ASSISTED MELANOMA EXTRAVASATION

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。癌症是美国第二大死亡原因。癌症转移的能力是癌症如此致命和治疗困难的原因之一。如果癌症可以包含在一个肿瘤中，那么存活率比癌症转移的患者要高得多。成功的转移需要一系列复杂的步骤。这些步骤可以概括为四个主要步骤：1）侵入，2）运输，3）粘附和4）外渗。抑制转移级联反应中的任何步骤将防止或减缓转移。本方案将研究黑色素瘤迁移发生的粘连和外渗步骤。粘附过程通过内皮细胞和粘附细胞之间的分子相互作用级联发生。粘附分子如选择素和整合素调节这一过程。因为内皮细胞和黑素瘤细胞都表达相对高水平的ICAM-1，而不是ICAM-1的相应配体MAC-1和LFA-1，所以桥（在这种情况下是白细胞）有助于实现两个细胞之间的有效粘附。已显示白细胞表达相对高值的LFA-1（一种ICAM-1配体）。使用流式细胞术来定量和表征黑色素瘤，人白细胞和内皮细胞上的粘附分子，以及体外流动迁移试验来测量迁移和外渗，研究人员可以检查有助于或阻碍转移级联的因素。

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.