Collagen type I expression in experimental anaplastic thyroid carcinoma:: Regulation and relevance for tumorigenicity
Collagen type I expression in experimental anaplastic thyroid carcinoma:: Regulation and relevance for tumorigenicity
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DOI：
10.1002/ijc.10181
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发表时间：
2002-03-10
影响因子：
6.4
通讯作者：
Rubin, K
中科院分区：
文献类型：
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作者：
Dahlman, T;Lammerts, E;Rubin, K
恶性实体瘤的纤维化在肿瘤病理生理学中起着重要作用。用6种特征性的甲状腺间变性癌（ATC）细胞系研究了ATC中I型胶原沉积的可能机制。这些细胞系中的三个产生1型胶原蛋白，作为一个组，当接种在无胸腺小鼠中时，具有较差的致瘤性。这组细胞在24只注射动物中的4只（17%）中产生肿瘤。表达前α I（I）胶原mRNA的癌细胞和基质细胞分散在由这些ATC细胞产生的肿瘤中。相反，3个非胶原生成ATC细胞系均具有致瘤性，整个组的肿瘤发生率为60%。在后一种肿瘤中，表达前α I（I）胶原mRNA的细胞局限于间质区室，与癌细胞胰岛界限分明。为了研究ATC细胞对成纤维细胞I型胶原合成的影响，我们使用在聚-（2-羟乙基甲基丙烯酸酯）（聚[HEMA]）包被的板上培养的AG 1518二倍体人成纤维细胞。该培养条件允许研究胶原mRNA翻译在I型胶原合成调节中的作用。来自6个ATC细胞系的条件培养基不影响胶原合成。ATC细胞系KAT-4刺激成纤维细胞合成胶原蛋白I型时，两种细胞类型共培养聚[HEMA]包被的基板。PDGF和TGF-β的特异性抑制剂减少了KAT 4癌细胞诱导的I型胶原合成刺激。我们的数据表明，I型胶原的癌细胞生产与致瘤性呈负相关，并形成一个明确的基质是肿瘤生长的重要性。此外，我们的数据表明，肿瘤细胞能够刺激胶原蛋白mRNA的翻译在基质成纤维细胞中直接细胞-细胞接触，至少部分地通过转移PDGF或TGF-β。(C)2002 Wiley-Liss，Inc.
Fibrosis in solid malignancies plays a significant role in tumor pathophysiology. Potential mechanisms for collagen type I deposition in anaplastic thyroid carcinoma (ATC) were investigated using 6 characterized ATC cell lines. Three of these cell lines, which produced collagen type 1, had, as a group, a poor tumorigenicity when inoculated in athymic mice. This group of cells generated tumors in 4 of 24 injected animals (17%). Pro-alphaI(I) collagen mRNA-expressing carcinoma and stromal cells were interdispersed in the tumors generated by these ATC cells. By contrast, the 3 noncollagen-producing ATC cell lines were all tumorigenic with a tumor take of 60% in the whole group. In the latter tumors, pro-alphaI(I) collagen mRNA-expressing cells were confined to the stromal compartment, well delineated from carcinoma cell islets. To study the influence of ATC cells on collagen type I synthesis by fibroblasts, we used AG 1518 diploid human fibroblasts cultured on poly-(2-hydroxyethyl methacrylate) (poly[HEMA])-coated plates. This culture condition allows the study of the effect of collagen mRNA translation in the regulation of collagen type I synthesis. Conditioned media from the 6 ATC cell lines did not influence collagen synthesis. The ATC cell line KAT-4 stimulated fibroblast synthesis of collagen type I when the two cell types were cocultured on poly[HEMA]-coated substrates. Specific inhibitors of PDGF and TGF-beta reduced the KAT 4 carcinoma cell-induced stimulation of collagen type I synthesis. Our data suggest that collagen type I production by carcinoma cells correlates negatively with tumorigenicity and that the formation of a well-defined stroma is of importance for tumor growth. Furthermore, our data suggest that tumor cells are able to stimulate collagen mRNA translation in stromal fibroblasts in direct cell-cell contact by, at least in part, transferring PDGF or TGF-beta. (C) 2002 Wiley-Liss, Inc.