CELLULAR AND MOLECULAR BASIS OF PROSTATE METASTASIS TO BONE

前列腺骨转移的细胞和分子基础

• 批准号: 6203263
• 负责人: Akepati Hari Reddi
• 金额: $ 16.85万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-08-04 至 2000-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6203263
• 关键词: biomarker; bone neoplasms; cellular oncology; clinical research; endothelin; growth factor; growth factor receptors; human subject; immunocytochemistry; laboratory rat; metastasis; molecular oncology; neoplasm /cancer diagnosis; prostate neoplasms; receptor expression; technology /technique development

The long-term goal of this research is to understand the mechanism(s) of metastasis of prostate cancer to bone. What is the cellular and molecular basis of the osteotropism of prostate cancer in humans? The bone morphogenetic proteins (BMPs) are prime candidates to play a role in prostate metastases and propensity to invade bone. The metastases of prostate to bone is characterized by osteosclerotic lesions and stimulation of osteoblast function. Current work has demonstrated both mRNA and protein for BMPs 4 and 7 in rat and human prostate. Very recently BMP-4 type I receptors were identified in osteoblasts. We will examine the hypothesis that BMP-4 acts on prostate in an autocrine manner via BMP-4 receptors. We will then investigate the hypothesis that metastatic prostate carcinoma over expresses BMP-4 receptor. A novel BMP type I receptor has been identified by PCR-based cloning strategy. We will determine the role of this putative receptor by functional assays. One of us has identified endothelin-1 gene and the protein in osseous metastases in human prostate cancer. Another investigator has identified a novel Bone and Prostate derived Growth Factor-1 (BPGF-1) and confers the metastatic phenotype to human LNCap cells. The specific aims of this proposal are: 1. Identification and characterization of BMP-4 and BMP-7 in rat and human prostate cancer. Examine the hypothesis that the BMP receptors are over-expressed in metastatic prostate carcinoma. 2. Determine the function of endothelin-1 in molecular physiology of osteoblastic response to prostate cancer and translate findings to clinical data as a marker of therapeutic response. 3. Investigate the role of BPGF-1 in bone metastases and translate findings to clinical data set as a biomarker of therapeutic response and intervention.

这项研究的长期目标是了解 前列腺癌转移到骨的机制。 是什么 前列腺癌向骨性的细胞和分子基础 在人类身上 骨形态发生蛋白（BMP）是主要的 在前列腺转移中发挥作用的候选人， 侵入骨。 前列腺骨转移的特点是 通过骨质疏松病变和刺激成骨细胞功能。 目前的工作已经证明了BMPs 4和BMPs 5的mRNA和蛋白质， 7在大鼠和人前列腺中。 最近BMP-4 I型受体 在成骨细胞中被鉴定。 我们将检验这个假设 BMP-4通过BMP-4以自分泌方式作用于前列腺， 受体。 然后我们将研究转移性肿瘤 前列腺癌过度表达BMP-4受体。 一种新的BMP类型， I受体已通过基于PCR的克隆策略鉴定。 我们 将通过功能测定来确定这种假定受体的作用， 分析。 我们中的一个已经鉴定了内皮素-1基因和蛋白质 在人类前列腺癌的骨转移中。 另一 研究人员发现了一种新的骨和前列腺衍生物， 生长因子-1（BPGF-1），并赋予转移表型， 人LNCap细胞。 这项建议的具体目标是： 1.大鼠骨形态发生蛋白-4和骨形态发生蛋白-7的鉴定与特性 和人类前列腺癌。 检验BMP 受体在转移性前列腺癌中过表达。 2.确定内皮素-1在分子生理学中的作用 成骨细胞对前列腺癌的反应， 临床数据作为治疗反应的标志。 3.研究BPGF-1在骨转移中的作用并将其翻译成 临床数据集的发现作为治疗的生物标志物 反应和干预。