STUDY OF MOLECULAR DYNAMICS IN LEUKOCYTE-ASSISTED MELANOMA EXTRAVASATION

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 癌症是美国第二大死因。癌症的转移能力是癌症如此致命和治疗困难的原因之一。如果癌症可以控制在一个肿瘤中，那么存活率比已经转移的癌症患者要高得多。成功的化生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)侵袭，2)运输，3)粘连和4)渗出。抑制转移级联过程中的任何一个步骤都将防止或减缓转移。 该方案将研究黑色素瘤发生迁移的粘连和外渗步骤。黏附过程通过内皮和黏附细胞之间的一系列分子相互作用发生。选择素和整合素等黏附分子调节这一过程。由于内皮细胞和黑色素瘤细胞都表达相对较高水平的细胞间黏附分子-1，而不是细胞间黏附分子-1 S对应的配体MAC-1和LFA-1，在这种情况下，一个桥梁，在这个例子中是一个白细胞，有助于实现两个细胞之间的有效黏附。已有研究表明，白细胞表达相对较高的ICAM-1配体LFA-1。使用流式细胞术来定量和表征黑色素瘤、人类白细胞和内皮细胞上的黏附分子，以及使用体外流动迁移实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.