Nomura Hitomi, Uzawa Katsuhiro, Ishigami Takashi, Kouzu Yukinao, Koike Hirofumi, Ogawara Katsunori, Siiba Masashi, Bukawa Hiroki, Yokoe Hidetaka, Kubosawa Hitoshi, Tanzawa Hideki
Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
BMC Cancer. 2008 Feb 1;8:39. doi: 10.1186/1471-2407-8-39.
Gelsolin-like actin-capping protein (CapG) is a ubiquitous gelsolin-family actin-modulating protein involved in cell signalling, receptor-mediated membrane ruffling, phagocytosis, and motility. CapG has generated great interest due to its oncogenic function in the control of cell migration or invasion in a variety of cancer cells. We previously applied proteomic methods to characterize differentially expressed proteins in oral squamous-cell carcinoma (OSCC) cells and detected significantly high expression levels of CapG in OSCC-derived cell lines compared to human normal oral keratinocytes. In the current study, to further determine the potential involvement of CapG in OSCC, we evaluated the status of CapG protein and mRNA expression in human oral premalignant lesions (OPLs) and primary OSCCs and correlated the results with clinicopathologic variables.
Matched normal and tumour tissue sections of 79 human primary OSCCs and 28 OPLs were analyzed for CapG expression by immunohistochemistry (IHC). Correlations between CapG-immunohistochemical staining scores of OSCCs and clinicopathologic features were evaluated by Fisher's exact test. Real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was used to estimate CapG expression at the mRNA level.
In IHC, substantial up-regulation of CapG protein was observed in primary OSCCs (52%) and OPLs (64%), whereas corresponding normal tissues showed consistently weak or absent immunoreactivity of CapG. qRT-PCR data were consistent with the protein expression status. Moreover, CapG expression was correlated with the TNM stage grading of OSCCs.
Our finding of frequent dysregulated expression of CapG in premalignant and malignant lesions together with an association with an advanced clinical disease stage suggests that CapG could contribute to cancer development and progression and that CapG may have potential as a biomarker and a therapeutic target for OSCC.
凝溶胶蛋白样肌动蛋白封端蛋白（CapG）是一种普遍存在的凝溶胶蛋白家族肌动蛋白调节蛋白，参与细胞信号传导、受体介导的膜褶皱、吞噬作用和细胞运动。CapG因其在多种癌细胞中控制细胞迁移或侵袭的致癌功能而备受关注。我们之前应用蛋白质组学方法对口腔鳞状细胞癌（OSCC）细胞中差异表达的蛋白质进行了表征，与人类正常口腔角质形成细胞相比，在OSCC衍生的细胞系中检测到CapG的表达水平显著升高。在本研究中，为了进一步确定CapG在OSCC中的潜在作用，我们评估了CapG蛋白和mRNA在人类口腔癌前病变（OPL）和原发性OSCC中的表达情况，并将结果与临床病理变量相关联。
采用免疫组织化学（IHC）方法分析79例人类原发性OSCC和28例OPL的配对正常和肿瘤组织切片中CapG的表达。通过Fisher精确检验评估OSCC的CapG免疫组织化学染色评分与临床病理特征之间的相关性。采用实时定量逆转录聚合酶链反应（qRT-PCR）在mRNA水平估计CapG的表达。
在免疫组织化学中，原发性OSCC（52%）和OPL（64%）中观察到CapG蛋白大量上调，而相应的正常组织中CapG的免疫反应性始终较弱或缺失。qRT-PCR数据与蛋白表达状态一致。此外，CapG表达与OSCC的TNM分期分级相关。
我们发现CapG在癌前和恶性病变中频繁表达失调，且与晚期临床疾病阶段相关，这表明CapG可能促进癌症的发生和发展，并且CapG可能具有作为OSCC生物标志物和治疗靶点的潜力。
