THE DESMOPLASTIC RESPONSE TO TUMOR INVASION

促结缔组织增生对肿瘤侵袭的反应是一个重要的， 我了解导致硬块的胶原宿主反应 出现多种癌症。 在人类乳腺癌中，大约80% 的病例与强烈的结缔组织增生有关，这种反应促进了 早期临床检测 这种反应的机制及其 对肿瘤侵袭和转移的影响尚不清楚，但先前的研究 已经表明促结缔组织增生反应由许多宿主组成， 肌成纤维细胞和独特的胶原蛋白分布， V型胶原蛋白。 这个研究项目的目的有三个方面。 的 第一个目的是表征和纯化肌成纤维细胞生长因子， 由侵袭性肿瘤细胞制造。 人乳腺癌组织 促结缔组织增生的品种和细胞系，如MCF-7和MDA-MB-134-VI将被 通过趋化性、有丝分裂发生和 成肌纤维细胞分化测定。 非促结缔组织增生性人乳腺 癌细胞（髓样型）和来源于它们的细胞系将作为 对照 第二个目的是进一步表征促结缔组织增生的 生物化学反应，特异性识别肿瘤抑制剂 蛋白酶如IV型胶原酶、组织蛋白酶和纤溶酶原 激活剂，所有这些都与侵入性过程有关。 促结缔组织增生的人类乳腺癌组织将再次成为 作为提取这些抑制剂的来源。 的 在促纤维增生细胞内大量蛋白酶抑制剂的证明 组织将表明，反应的一个目的是限制局部 肿瘤扩散。 本研究的最终目的是检验 结缔组织增生反应对远处转移的影响。 为了实现这一目标，一个新的 已经在C57 BL/6小鼠中开发了结缔组织增生的定量模型， 利用同基因可移植肿瘤BL 6黑素瘤，和 14C 腹腔内注入脯氨酸。 测量宿主胶原蛋白合成 在原发部位，用胶原合成阻滞剂干扰。 将确定对肺转移的影响。 长期 目的是了解结缔组织增生的机制和意义。 （一）

The desmoplastic response to tumor invasion is an important though poorly understood collagenous host reaction responsible for the hard lump appearance of many cancers. In human breast carcinoma, approximately 80% of cases are associated with intense desmoplasia, a response which promotes early clinical detection. Both the mechanism of this response and its effect on tumor invasion and metastasis are not known, but previous studies have indicated that the desmoplastic reaction is composed of numerous host myofibroblasts and a unique collagen profile with relatively high amounts of Type V collagen. The aims of this research project are three-fold. The first aim is to characterize and purify a myofibroblast growth factor elaborated by invasive tumor cells. Human breast carcinoma tissue of the desmoplastic variety and cell lines such as MCF-7 and MDA-MB-134-VI will be studied for the presence of such factors by chemotaxis, mitogenesis, and myofibroblast-differentiating assays. Non-desmoplastic human breast carcinoms (medullary type) and cell lines derived from them will serve as controls. The second aim is to further characterize the desmoplastic response biochemically, specifically identifying inhibitors to tumor proteases such as Type IV collagenase, cathepsins, and plasminogen activator, all of which have been implicated in the invasive process. Human breast carcinoma tissue of the desmoplastic variety again will serve as source from which to extract these inhibitors to invasion. The demonstration of high amounts of protease inhibitors within desmoplastic tissue would suggest that one purpose of the response is to limit the local spread of tumor. The final aim of this study is to examine the effect of the desmoplastic response on distant metastasis. To achieve this, a new quantitative model of desmoplasia has been developed in the C57 BL/6 mouse, utilizing the syngeneic transplantable tumor, BL6 melanoma, and 14C proline instilled intraperitoneally. Host collagen synthesis is measured at the primary site and perturbated with blockers of collagen synthesis. The effect on pulmonary metastases will be determined. The long-term purpose then is insight into the mechanism and meaning of desmoplasia. (A)