Siriwardena B S M S, Kudo Y, Ogawa I, Kitagawa M, Kitajima S, Hatano H, Tilakaratne W M, Miyauchi M, Takata T
Department of Oral Maxillofacial Pathobiology, Division of Frontier Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Hiroshima, Japan.
Br J Cancer. 2006 Nov 20;95(10):1396-403. doi: 10.1038/sj.bjc.6603431. Epub 2006 Oct 24.
Oral squamous-cell carcinoma (OSCC) is one of the most common types of human cancer. Typically OSCC cells show persistent invasion that frequently leads to local recurrence and distant lymphatic metastasis. We previously identified Periostin as the gene demonstrating the highest fold change expression in the invasive clone by comparing the transcriptional profile of parent OSCC cell line and a highly invasive clone. Here, we demonstrated that Periostin overexpression enhanced invasiveness in oral cancer cell lines. To know the role of Periostin in invasion, angiogenesis and metastasis in OSCC cases, we first examined the expression of Periostin mRNA in 31 OSCC cases by RT-PCR and Periostin protein in 74 OSCC cases by immunohistochemistry. Then, we compared the Periostin expression with invasion pattern, metastasis and blood vessel density. Periostin mRNA and protein overexpression were frequently found in OSCC cases and Periostin expression was well correlated with the invasion pattern and metastasis. Moreover, blood vessel density of Periostin-positive cases was higher than those of Periostin-negative cases. Interestingly, recombinant Periostin enhanced capillary formation in vitro in a concentration-dependant manner. In summary, these findings suggest that Periostin may promote invasion and angiogenesis in OSCC, and that Periostin can be a strong marker for prediction of metastasis in oral cancer patients.
口腔鳞状细胞癌(OSCC)是人类最常见的癌症类型之一。通常,OSCC细胞表现出持续的侵袭性,常常导致局部复发和远处淋巴转移。我们之前通过比较亲本OSCC细胞系和一个高侵袭性克隆的转录谱,鉴定出骨膜蛋白是在侵袭性克隆中表达变化倍数最高的基因。在此,我们证明骨膜蛋白的过表达增强了口腔癌细胞系的侵袭性。为了解骨膜蛋白在OSCC病例的侵袭、血管生成和转移中的作用,我们首先通过逆转录聚合酶链反应(RT-PCR)检测了31例OSCC病例中骨膜蛋白mRNA的表达,并通过免疫组织化学检测了74例OSCC病例中骨膜蛋白的表达。然后,我们将骨膜蛋白的表达与侵袭模式、转移和血管密度进行了比较。在OSCC病例中经常发现骨膜蛋白mRNA和蛋白的过表达,并且骨膜蛋白的表达与侵袭模式和转移密切相关。此外,骨膜蛋白阳性病例的血管密度高于骨膜蛋白阴性病例。有趣的是,重组骨膜蛋白在体外以浓度依赖的方式增强了毛细血管的形成。总之,这些发现表明骨膜蛋白可能促进OSCC的侵袭和血管生成,并且骨膜蛋白可以作为口腔癌患者转移预测的一个强有力的标志物。