FIBRONECTIN RECEPTORS AND CARCINOMA PROGRESSION

描述：申请人已经确定了Beta6亚基，并展示了它 与αv形成异二聚体，起纤维连接蛋白受体的作用。 此外，它的表达仅限于上皮细胞，并且急剧增加。 在发育过程中，伤口愈合、炎症，以及在恶性过程中 转型。αvbeta6在侵袭性组织中的表达最大 癌的边缘，申请人已经发现，转染Beta6 结肠癌细胞以胶原蛋白凝胶的形式促进其增殖。 基于这些数据，他假设Alphavbeta6起着关键作用 在体内癌细胞的侵袭性生长中。为了测试这一点 假设，他将研究癌细胞从新鲜的 将肿瘤移植到三维胶原-纤维连接蛋白基质中。他 将研究在这些条件下的alphavbeta6的分布，以及 确定抗αvbeta6抗体是否干扰迁移。他 然后将鉴定一系列表达癌基因的小鼠系，如 小鼠乳腺肿瘤控制下的c-neu、c-src和多瘤中T细胞 病毒推动者。αvbeta6在上述肿瘤组织中的分布 老鼠将被分析并与癌基因中的肿瘤进展相关 表情。最后，这些发展成Beta6阳性肿瘤的小鼠将是 与Beta6基因缺失的小鼠杂交，以确定在肿瘤方面是否存在一些差异 观察细胞行为。

DESCRIPTION: The applicant has identified the beta6 subunit, showed it forms heterodimers with alphav, and functions as a fibronectin receptor. Moreover, its expression is limited to epithelia and increases dramatically during development, wound healing, inflammation, and during malignant transformation. The largest expression of alphavbeta6 is found at invasive edges of carcinomas, and the applicant has found that transfection of beta6 in to colon cancer cells increases their proliferation in a collagen gel. Based on these data, he hypothesizes that alphavbeta6 plays a critical role in the invasive growth of carcinomas cells in vivo. To test this hypothesis, he will examine the migration of carcinoma cells out of freshly explanted tumors into a three dimensional collagen-fibronectin matrix. He will examine the distribution of alphavbeta6 under these conditions, and determine whether antibodies to alphavbeta6 interfere with migration. He will then characterize a series of mouse lines expressing oncogenes such as c-neu, c-src, and polyoma middle T under control of mouse mammary tumor virus promoter. The distribution of alphavbeta6 in tumor tissue of these mice will be analyzed and correlated with tumor progression in oncogene expression. Finally, these mice that develop beta6 positive tumors will be crossed with beta6 null mice, to determine whether some difference in tumor cell behavior is observed.