Ylipalosaari M, Thomas G J, Nystrom M, Salhimi S, Marshall J F, Huotari V, Tervahartiala T, Sorsa T, Salo T
Department of Diagnostics and Oral Medicine, Institute of Dentistry, University of Oulu and Oulu University Hospital, PO Box 5281, FIN-90014 Oulu, Finland.
Exp Cell Res. 2005 Oct 1;309(2):273-83. doi: 10.1016/j.yexcr.2005.06.008.
The integrin alphavbeta6, a receptor for fibronectin, vitronectin, tenascin and TGF-beta latency-associated peptide (LAP), is not detectable on normal oral epithelium but is neo-expressed in oral squamous cell carcinomas (OSCC) and epithelial dysplasia. Previously it has been shown that alphavbeta6 integrin can up-regulate MMP-3 and -9 expression in OSCC cells. Using beta6-transfected and control OSCC cells we demonstrate that alphavbeta6 integrin down-regulates MMP-13 expression at both mRNA and protein level. Although expressing less MMP-13, beta6-transfected cells were found to have similar collagenolytic activity as control cells and invade at similar levels through type I collagen. Growth of the tumour cells in organotypic culture and confocal microscopy confirmed low levels of MMP-13 in cells with high alphavbeta6 expression. Furthermore, human squamous cell carcinomas of the tongue with high expression of alphavbeta6 showed lower MMP-13 levels than carcinomas with low levels of alphavbeta6. Our results suggest that alphavbeta6 down-regulates MMP-13 expression in OSCC cells and that MMP-13 is not essential for the degradation of type I collagen by OSCC cells.
整合素αvβ6是纤连蛋白、玻连蛋白、肌腱蛋白和转化生长因子β潜伏相关肽（LAP）的受体，在正常口腔上皮中无法检测到，但在口腔鳞状细胞癌（OSCC）和上皮发育异常中重新表达。此前已表明，αvβ6整合素可上调OSCC细胞中基质金属蛋白酶-3（MMP-3）和基质金属蛋白酶-9（MMP-9）的表达。使用转染β6的OSCC细胞和对照OSCC细胞，我们证明αvβ6整合素在mRNA和蛋白质水平上均下调MMP-13的表达。尽管转染β6的细胞表达的MMP-13较少，但发现其胶原分解活性与对照细胞相似，并且通过I型胶原的侵袭水平也相似。肿瘤细胞在器官型培养中的生长和共聚焦显微镜检查证实，αvβ6高表达的细胞中MMP-13水平较低。此外，αvβ6高表达的人类舌鳞状细胞癌显示出比αvβ6低表达的癌更低的MMP-13水平。我们的结果表明，αvβ6在OSCC细胞中下调MMP-13的表达，并且MMP-13对于OSCC细胞降解I型胶原并非必不可少。
