Division of Surgical Oncology, Department of Surgery, University of Tokyo, Tokyo, Japan.
Cancer Sci. 2012 Nov;103(11):1961-6. doi: 10.1111/cas.12003. Epub 2012 Oct 15.
Malignant tumors are often associated with denervation, suggesting the functional implication of axonal guidance molecules in tumor growth. Here, we assessed the role of semaphorin 3C (sema3C) in the progression of gastric cancer. Immunohistochemistry of human samples revealed that sema3C was strongly expressed in neoplastic cells, especially at the invasion front. Stable transfection of target sequences of sema3C miRNA did not affect the in vitro proliferative activity of human gastric cancer AZ-521 cells. However, when the tumor growth was examined in vivo using an orthotopic model in nude mice, primary stomach tumors as well as metastatic liver tumors were significantly suppressed by sema3C silencing with the reduction of microvessel density. Immunostaining of primary tumor indicated the rate of Ki-67 positive carcinoma cells was decreased, whereas that of apoptotic cells was significantly increased in sema3C-silenced tumor. In addition, capillary-like tubular formation was reduced by the addition of culture media of sema3C miRNA cells compared with the media of control miRNA cells. Semaphorin 3C is positively expressed in gastric cancer cells and may be involved in tumor progression, presumably through the stimulation of angiogenesis.
恶性肿瘤常与去神经支配有关，这表明轴突导向分子在肿瘤生长中的功能意义。在这里，我们评估了 Sema 蛋白 3C（sema3C）在胃癌进展中的作用。对人样本的免疫组织化学分析表明，sema3C 在肿瘤细胞中强烈表达，特别是在侵袭前沿。sema3C miRNA 靶序列的稳定转染并不影响人胃癌 AZ-521 细胞的体外增殖活性。然而，当使用裸鼠的原位模型在体内检查肿瘤生长时，sema3C 沉默显著抑制了原发性胃肿瘤和转移性肝肿瘤，微血管密度降低。对原发性肿瘤的免疫染色表明，sema3C 沉默肿瘤中 Ki-67 阳性癌细胞的比率降低，而凋亡细胞的比率显著增加。此外，与对照 miRNA 细胞的培养基相比，sema3C miRNA 细胞的培养基中毛细管样管状结构的形成减少。Sema 蛋白 3C 在胃癌细胞中呈阳性表达，可能参与肿瘤进展，推测是通过刺激血管生成。
