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肿瘤促结缔组织增生的发病机制。II. 1号线和10号线豚鼠癌细胞及同基因成纤维细胞在体外合成的胶原蛋白

Pathogenesis of tumor desmoplasia. II. Collagens synthesized by line 1 and line 10 guinea pig carcinoma cells and by syngeneic fibroblasts in vitro.

作者信息

Form D M, VanDeWater L, Dvorak H F, Smith B D

出版信息

J Natl Cancer Inst. 1984 Nov;73(5):1207-14.

PMID:6092769
Abstract

For the investigation of the pathogenesis of desmoplasia, the capacities to synthesize collagen in vitro of 2 bile duct carcinomas (lines 1 and 10) of Sewall-Wright inbred strain 2 guinea pigs and of syngeneic dermal fibroblasts were studied. Line 10 cells synthesized collagen type IV as judged by sensitivity to bacterial collagenase, by immunoprecipitation, by migration of pro alpha (IV) chains and pepsin-resistant fragments on sodium dodecyl sulfate-polyacrylamide gels, and by immunofluorescence. Line 1 cells also synthesized small amounts of collagenase-sensitive protein. Neither line 1 nor line 10 cells synthesized detectable collagen type I, III, or V. Only about 1% of [14C]proline incorporated by tumor cells was found in collagenase-sensitive protein. In contrast, dermal fibroblasts synthesized 4 and 128 times as much collagenase-sensitive protein as line 10 and line 1 cells, respectively, amounting to 20% of total protein synthesized. Fibroblasts produced mostly collagen types I and III, in a ratio of 7:1, and smaller amounts of collagen type V. Thus lines 1 and 10 carcinoma cells produce primarily basement membrane collagen, whereas interstitial collagens, abundant in desmoplastic tumor stroma, are fibroblast products.

摘要

为了研究促结缔组织增生的发病机制,我们研究了2只Sewall-Wright近交系2豚鼠的胆管癌(细胞系1和10)以及同基因真皮成纤维细胞在体外合成胶原蛋白的能力。通过对细菌胶原酶的敏感性、免疫沉淀、原α(IV)链和耐胃蛋白酶片段在十二烷基硫酸钠-聚丙烯酰胺凝胶上的迁移以及免疫荧光判断,细胞系10细胞合成了IV型胶原。细胞系1细胞也合成了少量对胶原酶敏感的蛋白。细胞系1和细胞系10细胞均未合成可检测到的I型、III型或V型胶原。肿瘤细胞掺入的[14C]脯氨酸中,只有约1%存在于对胶原酶敏感的蛋白中。相比之下,真皮成纤维细胞合成的对胶原酶敏感的蛋白分别是细胞系10和细胞系1细胞的4倍和128倍,占合成总蛋白的20%。成纤维细胞主要产生I型和III型胶原,比例为7:1,还产生少量V型胶原。因此,细胞系1和细胞系10癌细胞主要产生基底膜胶原,而在促结缔组织增生性肿瘤基质中大量存在的间质胶原是成纤维细胞的产物。

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