DESMOPLASTIC RESPONSE TO TUMOR INVASION

促结缔组织增生对肿瘤侵袭的反应还知之甚少。 宿主肌成纤维细胞介导的胶原反应 许多人类癌症的“硬肿块”现象。这是竞争激烈的 更新换代将继续研究两者的发病机制 应答及其对肿瘤侵袭的影响 和转移。第一个基本目标将是进一步 25,000 mW肌成纤维细胞生长特性及纯化 因素，将其与已知的增长因素进行比较，展示了 此因子在发病机制中与体内反应有关 肌成纤维细胞表达c-myc、c-fos、弹性蛋白的研究 和V型胶原基因，并将在体内研究与 促结缔组织增生性c-Has-ras基因转染高p21MCF-7人 乳腺癌细胞株。第二个基本目标将是研究 分子量为40,000的促结缔组织生长抑制因子的作用 金属蛋白水解酶(DIMP)在促促筋膜促性腺反应中的作用 对肿瘤侵袭的部分但不是完全的抵抗 转移。这将涉及到DIMP与 金属蛋白酶组织抑制物(TIMP)及其临床评价 一种可能的机制，可以让肿瘤成功 胶原溶解即使是促结缔组织反应，也只是 部分成功地抑制了入侵，最终施加了 原发肿瘤亚群的选择压力 转移潜能增加。

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.