THE DESMOPLASTIC RESPONSE TO TUMOR INVASION

促结缔组织增生对肿瘤侵袭的反应是重要的，尽管不是很好。 了解硬肿块的胶原性宿主反应 许多癌症的出现。在人类乳腺癌中，大约80% 的病例与严重的促结缔组织增生症有关，这种反应促进 早期临床发现。这种反应的机制和它的 对肿瘤侵袭和转移的影响尚不清楚，但以前的研究 表明促结缔组织反应是由众多宿主组成的 肌成纤维细胞和相对高含量的独特的胶原蛋白 V型胶原蛋白。这个研究项目的目的有三个方面。这个 第一个目标是鉴定和纯化肌成纤维细胞生长因子 由侵袭性肿瘤细胞阐述。人乳腺癌组织的实验研究 促结缔组织变种和细胞系，如MCF-7和MDA-MB-134-VI 通过趋化、有丝分裂和细胞分裂来研究这些因子的存在 肌成纤维细胞分化试验。非促结缔组织增生性乳房 癌(髓质型)及其衍生的细胞系将作为 控制。第二个目标是进一步描述结缔组织 生化反应，特别是识别肿瘤的抑制物 蛋白酶，如IV型胶原酶、组织蛋白酶和纤溶酶原 激活剂，所有这些都与入侵过程有关。 人乳腺癌组织中的促结缔组织增生性变种将再次服务 作为提取这些入侵抑制物的来源。这个 结缔组织中含有大量的蛋白水解酶抑制剂 组织会认为，这种反应的一个目的是限制局部 肿瘤扩散。这项研究的最终目的是检查 促结缔组织增生反应对远处转移的影响。为了实现这一点，一种新的 在C57BL/6小鼠中建立了促结缔组织发育的定量模型。 利用同基因可移植肿瘤BL6黑色素瘤和14C 脯氨酸在腹膜腔内滴注。测量宿主胶原蛋白的合成 在原发部位，并受到胶原合成阻滞剂的干扰。 对肺转移的影响将被确定。长期的 目的是深入了解促结缔组织增生症的机制和意义。(A)

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)