Ohno Yoshio, Izumi Miki, Tachibana Masaaki, Kawamura Takeshi, Yoshioka Kunihiko, Aoyagi Teiichiro, Ohori Makoto, Namiki Kazunori, Sakamoto Noboru, Nakagami Yoshihiro, Hatano Tadashi, Akimoto Shingo, Nishimura Toshihide
Department of Urology, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo, Japan.
Oncol Rep. 2008 Sep;20(3):501-9.
Despite recent advances in molecular biology that have clarified the mechanisms involved in the metastasis of several types of cancer, the molecular mechanism underlying the metastasis of renal cell carcinoma (RCC) remains unclear. Two RCC cell lines were successfully established from the surgical specimens of a matched primary tumor and adrenal metastasis from the same RCC patient, and were designated as TMK-1P and TMK-1M, respectively. Extensive characterization was accomplished using various methods, including the Matrigel invasion assay, DNA microarray analysis and real-time reverse transcriptase (RT)-polymerase chain reaction (PCR). While TMK-1P grew faster than TMK-1M, the invasive ability of TMK-1M was higher than that of TMK-1P. DNA microarray analysis showed a large differential expression of genes related to cell adhesion and the extracellular matrix molecules of which hexabrachion (tenascin-C), epidermal growth factor receptor, cadherin-6, and beta1-catenin were down-regulated, and the 67 kDa laminin receptor 1 and transforming growth factor-beta-induced 68 kDa protein (betaig-h3) were up-regulated in TMK-1M. Real-time RT-PCR analysis confirmed this differential gene expression between the two cell lines. The RCC cell lines may be useful in studying tumor invasion and screening markers for metastasis.
尽管分子生物学最近取得了进展,已阐明了几种癌症转移所涉及的机制,但肾细胞癌(RCC)转移的分子机制仍不清楚。从同一RCC患者的匹配原发性肿瘤和肾上腺转移灶的手术标本中成功建立了两种RCC细胞系,分别命名为TMK-1P和TMK-1M。使用多种方法进行了广泛的表征,包括基质胶侵袭试验、DNA微阵列分析和实时逆转录(RT)-聚合酶链反应(PCR)。虽然TMK-1P比TMK-1M生长得更快,但TMK-1M的侵袭能力高于TMK-1P。DNA微阵列分析显示,与细胞粘附和细胞外基质分子相关的基因存在大量差异表达,其中六臂蛋白(腱生蛋白-C)、表皮生长因子受体、钙粘蛋白-6和β-连环蛋白下调,而67 kDa层粘连蛋白受体1和转化生长因子-β诱导的68 kDa蛋白(βig-h3)在TMK-1M中上调。实时RT-PCR分析证实了这两种细胞系之间的差异基因表达。RCC细胞系可能有助于研究肿瘤侵袭和转移的筛选标志物。