DESMOPLASTIC RESPONSE TO TUMOR INVASION

对肿瘤侵袭的促纤维化反应

• 批准号: 3179899
• 负责人: Sanford Howard Barsky
• 金额: $ 7.54万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-07-01 至 1993-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3179899
• 关键词: amnion; athymic mouse; breast neoplasms; collagen; collagenase; enzyme inhibitors; extracellular matrix; fibroblast growth factor; gene expression; growth factor; human pregnant subject; human tissue; immunofluorescence technique; ion exchange chromatography; laboratory mouse; lung neoplasms; melanoma; metalloenzyme; metastasis; neoplasm /cancer invasiveness; neoplastic cell; protease inhibitor; protein biosynthesis; radiotracer

The desmoplastic response to tumor invasion is a poorly understood host myofibroblast-mediated collagenous response responsible for the "hard lump" appearance of many human cancers. This competitive renewal will continue to study both the pathogenesis of the response as well as the effects of the response on tumor invasion and metastasis. The first basic aim will be to further characterize and purify the 25,000 M.W. myofibroblast growth factor, compare it to known growth factors, demonstrate a role for this factor in the pathogenesis of the response with in vivo studies of myofibroblast expression of c-myc, c-fos, elastin, Type I, and Type V collagen genes and will in vivo studies with the desmoplasia-inducing c-Has-ras transfected high p21 MCF-7 human breast carcinoma cell line. The second basic aim will be to study the role of the 40,000 M.W. desmoplastic inhibitor of metalloproteinases (DIMP) in conferring to the desmopastic response a partial but not total resistance to tumor invasion and metastasis. This will involve a detailed comparison of DIMP with TIMP (tissue inhibitor of metalloproteinases) and an evaluation of a possible mechanism which would allow successful tumor collagenolysis even whether the desmoplastic response, being only partially successful in inhibiting invasion, ultimately exerts selection pressure for subpopulations of the primary tumor with increased metastatic potential.

促结缔组织增生对肿瘤侵袭的反应是一个知之甚少的 宿主成肌纤维细胞介导胶原反应 许多人类癌症的“硬块”外观。 这个竞争激烈 更新将继续研究的发病机制， 反应以及反应对肿瘤侵袭的影响 和转移。 第一个基本目标将是进一步 表征和纯化25，000 M.W.肌成纤维细胞生长 因子，将其与已知的生长因子进行比较，证明其对 这种因素在发病机制中的反应与体内 肌成纤维细胞c-myc、c-fos、弹性蛋白表达的研究 I型和V型胶原基因，并将在体内研究与 促结缔组织形成的c-Has-ras转染高p21 MCF-7人 乳腺癌细胞系 第二个基本目标是研究 40,000兆瓦的作用。促结缔组织增生抑制剂 金属蛋白酶（DIMP）在促结缔组织增生反应中的作用 对肿瘤侵袭的部分但非全部抵抗， 转移 这将涉及DIMP与 TIMP（金属蛋白酶组织抑制剂）和评估 一种可能的机制， 胶原溶解甚至是否促结缔组织增生反应， 部分成功地抑制了入侵， 原发性肿瘤亚群的选择压力， 增加转移潜能。