DISTRIBUTION AND FUNCTION OF THE INTEGRIN ANDYB8

整合素受体在细胞黏附、迁移、 侵袭、转移、归巢和信号传递。这些细胞表面受体 由单个α亚基和单个β亚基组成，并结合到 细胞外基质成分，如纤维连接蛋白、玻璃体连接蛋白、层粘连蛋白 和胶原蛋白。表达时含有α-v亚基的整合素 黑色素瘤等恶性肿瘤在肿瘤的侵袭和转移中起着重要作用。我 已经描述了最近发现的包含以下内容的α-v的表达 整合素受体α-v-beta8在黑色素瘤细胞系中的表达 将其描述为一种玻璃连结蛋白受体。阿尔法-v-贝塔8是如何 有助于黑色素瘤细胞黏附、迁移 并对维他林有反应而增殖吗？Alpha-v-beta8是否与 除了Vitronectin以外的其他配体？Beta8的独特结构是如何 与它的功能有关吗？为什么黑色素瘤细胞表达多个 Vitronectin受体及其表达与血管内皮生长因子 侵袭性表型？为了回答这些问题，我将评估函数 在黑色素瘤细胞系中正常表达，在黑色素瘤中过表达 正常不表达β-8的黑色素瘤细胞系 亚单位。我将评估Beta8转基因细胞的能力 在黏附和迁移试验中黏附和迁移到Vitronectin上。 有证据表明，整合素可以刺激细胞增殖。这就做 用Beta8、转基因黑色素瘤和293细胞评价细胞 三维凝胶体系中的增殖。我要测试你的能力 转Beta8基因的黑色素瘤细胞和293细胞的跨膜侵袭 正如所说的那样，各种各样的入侵。最后，我将表演 黑色素瘤标本的免疫组织化学分析，并将评估a-v 整合素表达。这些研究将为 一种新发现的整合素的功能及其生物学意义 黏附受体，并将提供必要的优秀训练 向科学独立过渡。

Integrin receptors play an important role in cell adhesion, migration, invasion, metastasis, homing and signalling. These cell surface receptors are composed of a single alpha and a single beta subunit and bind to extracellular matrix components such as fibronectin, vitronectin, laminin and collagen. Integrins containing the alpha-v subunit when expressed in malignancies such as melanoma play a role in invasion and metastasis. I have described the expression of a recently identified alpha-v containing integrin receptor, alpha-v-beta8, in melanoma cell lines and have characterized it as a vitronectin receptor. How does alpha-v-beta8 contribute to the ability of the melanoma cell to adhere to, migrate on and proliferate in response to vitronectin? Does alpha-v-beta8 bind to ligands other than vitronectin? How does the unique structure of beta8 relate to its function? Why does the melanoma cell express multiple vitronectin receptors and how does their expression correlate to the invasive phenotype? To answer these questions I will evaluate the function of beta8 normally expressed in melanoma cell lines and overexpressed in transfected melanoma cell lines which normally do not express the beta8 subunit. I will evaluate the ability of the beta8 transfected cells to adhere to and to migrate on vitronectin in adhesion and migration assays. Evidence has shown that integrins may stimulate cell proliferation. I will use beta8, transfected melanoma and 293 cells to evaluate cell proliferation in 3 dimensional gel systems. I will test the ability of beta8 transfected melanoma and 293 cells to invade through membranes using a variety of invasion as says. Finally, I will perform immunohistochemical analysis on melanoma specimens and will assess a-v integrin expression. These studies will provide valuable information into the function and biologic importance of a newly described integrin adhesion receptor and will provide the excellent training necessary for making the transition to scientific independence.