Cellular Adhesion and Prostate Tumor Progression

细胞粘附和前列腺肿瘤进展

• 批准号: 6990126
• 负责人: ANNE E CRESS
• 金额: $ 11.65万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-19 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6990126
• 关键词: SCID mouse; biological signal transduction; cell adhesion; cell migration; combinatorial chemistry; flow cytometry; gene expression; human tissue; in situ hybridization; integrins; laminin; ligands; male; molecular oncology; neoplasm /cancer invasiveness; neoplastic process; phenotype; prostate neoplasms; protein structure function; receptor expression; scanning electron microscopy; transfection

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.

待检验的假设是，a6及其变体a6 p与人层粘连蛋白的侵袭有关。 5和层粘连蛋白10/11包被的结构。癌细胞上的a6 p变体用于保留细胞内结构和信号特征以用于迁移和侵袭。a6 p被认为是通过细胞表面的受体加工而产生的。肿瘤细胞在层粘连蛋白5和层粘连蛋白10/11上的粘附特性将被肽或小分子中断。建议的具体目标如下： 1.确定a6 pb 1或a6 pb 4变体的功能作用。目标包括确定 分别在粘着斑或半桥粒中的变异体的分布以及层粘连蛋白5和层粘连蛋白10/11上的细胞粘附、迁移或侵袭的改变。 2.确定α 6 β整联蛋白产生的机制是否是由于受体加工。 3.确定通过d-氨基肽或小分子阻断细胞粘附是否会改变培养中的人前列腺癌细胞、人器官培养中的前列腺细胞和/或前列腺癌异种移植物的生长、侵袭或存活表型。