Department of Dermatology, PEDEGO Research Unit, Oulu Center for Cell-Matrix Research, MRC Oulu, University of Oulu and Oulu University Hospital, Finland.
Skin Cancer Unit of the Dermatology Department, Medical Faculty, West German Cancer Center, University of Duisburg-Essen, Germany.
Sci Rep. 2017 Mar 22;7:45057. doi: 10.1038/srep45057.
Collagen XVII and integrin α6β4 have well-established roles as epithelial adhesion molecules. Their binding partner laminin 332 as well as integrin α6β4 are largely recognized to promote invasion and metastasis in various cancers, and collagen XVII is essential for the survival of colon and lung cancer stem cells. We have studied the expression of laminin γ2, collagen XVII and integrin β4 in tissue microarray samples of squamous cell carcinoma (SCC) and its precursors, actinic keratosis and Bowen's disease. The expression of laminin γ2 was highest in SCC samples, whereas the expression of collagen XVII and integrin β4 varied greatly in SCC and its precursors. Collagen XVII and integrin β4 were also expressed in SCC cell lines. Virus-mediated RNAi knockdown of collagen XVII and integrin β4 reduced the migration of less aggressive SCC-25 cells in horizontal scratch wound healing assay. Additionally, in a 3D organotypic myoma invasion assay the loss of collagen XVII or integrin β4 suppressed equally the migration and invasion of SCC-25 cells whereas there was no effect on the most aggressive HSC-3 cells. Variable expression patterns and results in migration and invasion assays suggest that collagen XVII and integrin β4 contribute to SCC tumorigenesis.
XVII 型胶原和整合素 α6β4 是上皮细胞黏附分子,其作用已得到充分证实。它们的结合伴侣层粘连蛋白 332 以及整合素 α6β4 被广泛认为可促进多种癌症的侵袭和转移,而 XVII 型胶原对于结肠和肺癌干细胞的存活是必需的。我们研究了组织微阵列样本中鳞状细胞癌(SCC)及其前体光化性角化病和 Bowen 病中层粘连蛋白 γ2、XVII 型胶原和整合素 β4 的表达。层粘连蛋白 γ2 在 SCC 样本中的表达最高,而 XVII 型胶原和整合素 β4 在 SCC 和其前体中的表达差异很大。XVII 型胶原和整合素 β4 也在 SCC 细胞系中表达。病毒介导的 RNAi 敲低 XVII 型胶原和整合素 β4 可减少侵袭性较弱的 SCC-25 细胞在水平划痕愈合测定中的迁移。此外,在 3D 器官样肌瘤侵袭测定中,缺失 XVII 型胶原或整合素 β4 同样抑制 SCC-25 细胞的迁移和侵袭,但对侵袭性最强的 HSC-3 细胞没有影响。迁移和侵袭测定中的可变表达模式和结果表明,XVII 型胶原和整合素 β4 有助于 SCC 的肿瘤发生。