Liu H, Chen B, Zardi L, Ramos D M
Department of Traditional Chinese Medicine and Oral Medicine, School of Stomatology, Beijing Medical University, PR China.
Int J Cancer. 1998 Oct 5;78(2):261-7. doi: 10.1002/(sici)1097-0215(19981005)78:2<261::aid-ijc22>3.0.co;2-c.
We have shown that a fibronectin (FN) matrix is required for the organization of tenascin-C (TN-C) matrices by peritumor fibroblasts (PTF) cultured from tissue surrounding oral squamous-cell carcinoma (SCC). In the present study, we detected alternatively spliced FN containing both the EDA and EDB domains decorating the reactive stroma adjacent to the invading tumor nests in oral SCC biopsies. In vitro, PTF cells organized an extensive FN matrix rich in the EDA domain and containing a small amount of EDB. In contrast, normal human fibroblasts deposited a FN matrix which expressed only the EDA domain. PTF-conditioned medium (CM), shown to enhance migration of oral SCC cells on TN-C, was found to enhance their migration on FN and invasion of a reconstituted basement membrane. Addition of antibodies to FN to the PTF-CM inhibited SCC-cell migration on TN-C, and depletion of FN from the PTF-CM abolished its ability to induce migration or invasion by oral SCC cells, suggesting that FN promotes the migration and invasion of oral SCC cells. Western blots of the PTF-CM identified FN containing the EDA but not the EDB domain. When soluble FN was added to the control medium in the lower chamber of the Transwell system, SCC-cell migration increased significantly. These results demonstrate that both the EDA and the EDB domains of FN are expressed in the extracellular matrix of oral SCC in vivo and PTF in vitro and indicate that FN is the probable chemotactic factor in the PTF-conditioned medium.
我们已经表明，来自口腔鳞状细胞癌（SCC）周围组织培养的肿瘤周围成纤维细胞（PTF）构建腱生蛋白-C（TN-C）基质需要纤连蛋白（FN）基质。在本研究中，我们在口腔SCC活检组织中检测到含有EDA和EDB结构域的选择性剪接FN，其修饰侵袭性肿瘤巢附近的反应性基质。在体外，PTF细胞构建了富含EDA结构域且含有少量EDB的广泛FN基质。相比之下，正常人成纤维细胞沉积的FN基质仅表达EDA结构域。已证明PTF条件培养基（CM）可增强口腔SCC细胞在TN-C上的迁移，发现其可增强细胞在FN上的迁移及对重组基底膜的侵袭。向PTF-CM中添加FN抗体可抑制SCC细胞在TN-C上的迁移，从PTF-CM中去除FN则消除了其诱导口腔SCC细胞迁移或侵袭的能力，这表明FN促进口腔SCC细胞的迁移和侵袭。PTF-CM的蛋白质免疫印迹鉴定出含有EDA但不含EDB结构域的FN。当将可溶性FN添加到Transwell系统下室的对照培养基中时，SCC细胞迁移显著增加。这些结果表明，FN的EDA和EDB结构域在体内口腔SCC的细胞外基质以及体外PTF中均有表达，并表明FN可能是PTF条件培养基中的趋化因子。
