Identification of Proteins Mediating Prostate Cancer

介导前列腺癌的蛋白质的鉴定

• 批准号: 7016297
• 负责人: Mikhail G Kolonin
• 金额: $ 12.6万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-02-15 至 2007-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7016297
• 关键词: biochemistry; biomarker; bone marrow; cell cell interaction; cell surface receptors; clinical research; complementary DNA; genetic library; high throughput technology; human subject; ligands; metastasis; nucleic acid sequence; polymerase chain reaction; prostate neoplasms; proteins; tissue /cell culture

DESCRIPTION (provided by applicant): Molecular mechanisms of prostate cancer metastasis to the bone are not well understood, and the ligand-receptor systems mediating this process are largely unknown. Proposed here is an integrated approach based on powerful platform technologies that will be used to dissect the molecular mechanisms of interaction between metastatic prostate cancer cells and the bone marrow. Recently established screening of random peptide phage display libraries in cancer patients enables quick isolation of ligands that can home to the vasculature of specific tissues. We propose to use bone marrow-homing peptides isolated in prostate cancer patients as leads for identification of human cell surface proteins mediating bone metastasis expressed by malignant prostate tumors. Peptide motifs homing to human bone marrow will be isolated using an enhanced in vivo phage display assay, parallel biopanning. The corresponding prostate cancer cell surface proteins containing the bone marrow-homing motifs will be identified using a specially designed bioinformatics platform. For several peptides validated to have high affinity and specificity for bone marrow, based on their testing in culture and in situ, we propose to identify the corresponding bone marrow receptors for the putative prostate cancer markers. For receptor identification, we will use a combination of previously established candidate receptor approach, conventional biochemistry, and the phage two-hybrid system: a recently developed assay for isolation of interacting proteins. As a result, this study is expected to identify at least one or two ligand-receptor pairs, which may be established or yet uncharacterized proteins that mediate the homing of metastatic prostate cancer cells to the bone. In the future, the identified molecules can be validated as potential biomedical targets for prostate cancer profiling and intervention by determining selectivity of their expression in the context of the disease. Upon optimization, this approach may be streamlined to systematically profile the molecular diversity of tumor cell-bone marrow nteractions for assessment of prognosis and/or for treatment of metastatic prostate cancer in individual patients.

描述（由申请人提供）：前列腺癌向骨骼的分子机制尚不清楚，并且介导该过程的配体受体系统在很大程度上尚不清楚。 这里提出的是一种基于强大平台技术的综合方法，该方法将用于剖析转移性前列腺癌细胞和骨髓之间相互作用的分子机制。 最近在癌症患者中对随机肽噬菌体展示文库进行了筛查，可以快速隔离可以归为特定组织脉管系统的配体。 我们建议使用在前列腺癌患者中分离的骨髓含肽作为鉴定由恶性前列腺肿瘤表达的骨转移的人类细胞表面蛋白。 使用增强的体内噬菌体显示测定法，平行生物塑料，将分离到人骨髓中的肽基序。 将使用特殊设计的生物信息学平台鉴定出含有骨髓含有骨含有骨的前列腺癌细胞表面蛋白。 对于经过验证的几种肽对骨髓具有高亲和力和特异性，根据其在培养物的测试和原位的测试，我们建议确定推定的前列腺癌标志物的相应骨髓受体。 对于受体鉴定，我们将使用先前建立的候选受体方法，常规生物化学和噬菌体两杂交系统的组合：最近开发的用于隔离相互作用蛋白质的测定法。 结果，这项研究有望鉴定至少一个或两个配体 - 受体对，可以建立或尚未表征蛋白质，这些蛋白质可以介导转移性前列腺癌细胞的归位为骨骼。 将来，可以通过在疾病背景下确定其表达的选择性来证实所鉴定的分子作为前列腺癌分析和干预的潜在生物医学靶标。 一旦优化，该方法可能会精简以系统地介绍肿瘤细胞骨骨髓的分子多样性，以评估预后和/或治疗个别患者的转移性前列腺癌。