Hatano Hiroko, Kudo Yasusei, Ogawa Ikuko, Tsunematsu Takaaki, Kikuchi Akira, Abiko Yoshimitsu, Takata Takashi
Department of Oral and Maxillofacial Pathobiology, Division of Frontier Medical Science, Hiroshima University Hospital, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, Japan.
Clin Cancer Res. 2008 Oct 1;14(19):6097-105. doi: 10.1158/1078-0432.CCR-07-4761.
Head and neck squamous cell carcinoma (HNSCC) shows persistent invasion that frequently leads to local recurrence and distant lymphatic metastasis. However, molecular mechanisms associated with invasion of HNSCC remain poorly understood. We identified IFN-induced transmembrane protein 1 (IFITM1) as a candidate gene for promoting the invasion of HNSCC by comparing the gene expression profiles between parent and a highly invasive clone. Therefore, we examined the role of IFITM1 in the invasion of HNSCC.
IFITM1 expression was examined in HNSCC cell lines and cases by reverse transcription-PCR and immunohistochemistry. IFITM1 overexpressing and knockdown cells were generated, and the invasiveness of these cells was examined by in vitro invasion assay. Gene expression profiling of HNSCC cells overexpressing IFITM1 versus control cells was examined by microarray.
HNSCC cells expressed IFITM1 mRNA at higher levels, whereas normal cells did not. By immunohistochemistry, IFITM1 expression was observed in early invasive HNSCC and invasive HNSCC. Interestingly, IFITM1 was expressed at the invasive front of early invasive HNSCC, and higher expression of IFITM1 was found in invasive HNSCC. In fact, IFITM1 overexpression promoted and IFITM1 knockdown suppressed the invasion of HNSCC cells in vitro. Gene expression profiling of HNSCC cells overexpressing IFITM1 versus control cells revealed that several genes, including matrix metalloproteinase, were up-regulated in IFITM1 overexpressing cells.
Our findings suggest that IFITM1 plays an important role for the invasion at the early stage of HNSCC progression and that IFITM1 can be a therapeutic target for HNSCC.
头颈部鳞状细胞癌（HNSCC）表现出持续的侵袭性，常导致局部复发和远处淋巴转移。然而，与HNSCC侵袭相关的分子机制仍知之甚少。通过比较亲本细胞和高侵袭性克隆之间的基因表达谱，我们确定干扰素诱导跨膜蛋白1（IFITM1）为促进HNSCC侵袭的候选基因。因此，我们研究了IFITM1在HNSCC侵袭中的作用。
通过逆转录PCR和免疫组织化学检测HNSCC细胞系和病例中IFITM1的表达。构建了IFITM1过表达和敲低的细胞，并通过体外侵袭实验检测这些细胞的侵袭性。通过微阵列检测过表达IFITM1的HNSCC细胞与对照细胞的基因表达谱。
HNSCC细胞中IFITM1 mRNA表达水平较高，而正常细胞则不表达。通过免疫组织化学，在早期侵袭性HNSCC和侵袭性HNSCC中观察到IFITM1表达。有趣的是，IFITM1在早期侵袭性HNSCC的侵袭前沿表达，且在侵袭性HNSCC中发现IFITM1表达更高。事实上，IFITM1过表达促进了HNSCC细胞的侵袭，而IFITM1敲低则抑制了其侵袭。过表达IFITM1的HNSCC细胞与对照细胞的基因表达谱显示，包括基质金属蛋白酶在内的几个基因在IFITM1过表达细胞中上调。
我们的研究结果表明，IFITM1在HNSCC进展的早期侵袭中起重要作用，且IFITM1可成为HNSCC的治疗靶点。
