GROWTH FACTORS IN THE PROSTATE: AN IN VITRO MODEL

前列腺中的生长因子：体外模型

• 批准号: 2147263
• 负责人: Donna M Peehl
• 金额: $ 19.82万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-09-30 至 1996-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2147263
• 关键词: biopsy; cell growth regulation; gene expression; growth factor; growth factor receptors; human tissue; physical chemical interaction; prostate neoplasms; receptor expression; tissue /cell culture; tissue /cell preparation; tumor antigens; ultrasound; vitamin A deficiency; vitamin D

The etiology of prostate cancer is essentially not understood. Molecular mechanisms responsible for initiation and progression remain largely unknown, and the endogenous or systemic factors involved in mediating rapid and metastatic growth are generally unidentified. It is clear, however, that major determinants of the malignant phenotype depend on various growth-stimulatory and inhibitory factors and their receptors whose inappropriate expression or loss disrupt normal regulation of cell proliferation and differentiation. Tissue culture is perhaps our most versatile tool for studying the expression and interaction of growth factors in living cells. We hypothesize that the continued development of optimal cell culture techniques and in-depth study of human prostate cell cultures derived from normal and malignant tissues will lead to the recognition of factors involved in the biologic progression of the malignant phenotype. Using the established and efficient retrieval, culture and analysis techniques that we have refined during the past ten years, we propose to maintain and expand our characterization of the response to and expression of growth factors by monolayer cultures of prostatic epithelial cells derived from normal tissues and moderate-grade cancers. We further propose to increase the diversity of malignant tissue examined by expanding our studies to cell cultures derived from high-grade cancers, which will be accessed by ultrasound-guided needle biopsies. The phenotype of these cells will be compared to that of cells obtained from normal tissues and moderate-grade cancers. In addition, we plan to optimize conditions for 3-dimensional growth of prostate cells. We project that the phenotype and response to and expression of growth factors of cells in 3-dimensional culture will differ from that in monolayer culture, and will be more reflective of the in vivo situation. Our previous studies have shown important regulatory roles for epidermal growth factor, fibroblast growth factors, insulin-like growth factors, prostate specific antigen, transforming growth factor-B, vitamin A, and vitamin D. Our future efforts will emphasize study of the interactions of these factors and their receptors in monolayer and 3-dimensional cultures of normal and malignant cell populations at the molecular and cellular levels. Our ultimate goal is an inclusive definition of the autocrine, paracrine and endocrine pathways of growth regulation in the human prostate and recognition of deregulation in prostate cancer. Our multifaceted approach should provide information which will facilitate the logical design of new preventative, diagnostic, and therapeutic strategies.

前列腺癌的病因基本上不清楚。分子 负责启动和进展的机制仍然主要是 未知，以及参与调解的内源性或系统性因素 快速和转移性生长通常是未鉴定的。很明显， 然而，恶性表型主要决定因素取决于 各种生长刺激和抑制因子及其受体 其不适当的表达或缺失会破坏细胞的正常调节 增殖和分化。组织培养也许是我们最 研究生长的表达和相互作用的多功能工具 活细胞中的因子。我们假设， 优化细胞培养技术和深入研究人前列腺细胞 来自正常和恶性组织的培养物将导致 认识到的因素参与的生物进展， 恶性表型使用已建立的有效检索， 我们在过去十年中改进的文化和分析技术， 多年来，我们建议保持和扩大我们的特点， 单层培养物对生长因子的反应和表达 前列腺上皮细胞来源于正常组织和中度 癌的我们进一步建议增加恶性组织的多样性 通过将我们的研究扩展到来自高级别细胞的细胞培养来检查 癌症，这将通过超声引导的针活检访问。的 将这些细胞的表型与从以下获得的细胞的表型进行比较： 正常组织和中度癌症。此外，我们计划 优化前列腺细胞三维生长的条件。我们预计 这些细胞的表型、对生长因子的反应和表达， 三维培养中的细胞将不同于单层培养中的细胞， 并且将更能反映体内情况。我们以前的研究 已经显示出对表皮生长因子的重要调节作用， 成纤维细胞生长因子，胰岛素样生长因子，前列腺特异性 抗原、转化生长因子-B、维生素A和维生素D。我们 今后的工作重点将是研究这些因素之间的相互作用 和它们的受体在单层和三维培养的正常和 恶性细胞群体在分子和细胞水平。我们 最终目标是自分泌、旁分泌和 人前列腺生长调节的内分泌途径， 认识到前列腺癌的失调。我们的多方面方法 应提供资料，以促进新的逻辑设计 预防、诊断和治疗策略。