Cellular Adhesion and Prostate Tumor Progression

需要检验的假设是a6及其变异体a6p与人类层粘连蛋白的侵袭有关。 5和层粘连蛋白10/11包被结构。癌细胞上的a6p变异体起到保护细胞内结构和信号特征以进行迁移和侵袭的作用。A6p被认为是通过细胞表面的受体处理而产生的。肿瘤细胞对层粘连蛋白5和层粘连蛋白10/11的黏附特性会被多肽或小分子干扰。提出了以下具体目标： 1.确定a6pb1或a6pb4变异体的功能作用。目标包括确定 变异体在局部黏附部位或半桥粒中的分布以及细胞对层粘连蛋白5和层粘连蛋白10/11的黏附、迁移或侵袭的改变。 2.确定a-6p整合素的产生机制是否与受体的加工有关。 3.确定d-氨基肽或小分子阻断细胞黏附是否会改变培养的人前列腺癌细胞、人体器官培养的前列腺癌细胞和/或前列腺癌异种移植瘤的生长、侵袭或存活表型。

The hypothesis to be tested is that the a6 and its variant a6p the invasion of human laminin 5 and laminin 10/11 coated structures. The a6p variant on the cancer cells acts to preserve the intracellular structural and signaling features for migration and invasion. The a6p is proposed to arise by receptor processing on the cell surface. The adhesion properties of the tumor cells on laminin 5 and laminin 10/11 will be interrupted by peptides or small molecules. The following specific aims are proposed: 1. Determine the functional role of the a6pb1 or a6pb4 variants. The aim includes determining the distribution of the variants in the focal adhesion site or hemidesmosome respectively and alteration of cellular adhesion, migration or invasion on laminin 5 and laminin 10/11. 2. Determine whether the mechanism of a6p integrin production is due to receptor processing. 3. Determine if blocking cell adhesion by d-amino peptides or small molecules will alter the growth, invasion or the survival phenotype of human prostate cancer cells in culture, prostate cells in a human organ culture and or a prostate cancer xenograft.