Li Chao, Gu Youling, Andrade Dario, Liu Yuechueng
Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73190, USA.
J Exp Ther Oncol. 2009;8(2):167-75.
Sindbis virus (SIN), a member of the Togaviridae family, infects a broad range of cells and has been shown to be an effective anti-tumor agent. The infection efficiency of the virus, however, varies greatly among target cells. In this report, we compared the ability of SIN to infect colorectal cancer cells and cells of other cancer origin. While tumor cells from breast, leukemia, and prostate cancers were largely resistant to SIN infection, nine of the ten colorectal cancer cell lines tested were sensitive to SIN infection. Moreover, SIN susceptibility correlated with the metastatic potential of the colorectal cancer cells. Two highly aggressive and invasive cell lines, SW620 and COLO-320DM were the most sensitive to SIN infection. Similarly, SIN preferentially targeted metastatic tumor cells in a mouse xenograft model for colon cancer progression. The higher infection rate was not due to increased expression of the 67kD laminin receptor, a specific receptor for SIN infection, although viral attachment and entry were markedly enhanced in SW620 cells. These results suggest that SIN may employ a novel cell attachment/entry mechanism during infection, allowing selective targeting of colorectal cancer cells.
辛德毕斯病毒(SIN)是披膜病毒科的成员,可感染多种细胞,并已被证明是一种有效的抗肿瘤药物。然而,该病毒的感染效率在靶细胞之间差异很大。在本报告中,我们比较了SIN感染结肠癌细胞和其他癌症来源细胞的能力。虽然来自乳腺癌、白血病和前列腺癌的肿瘤细胞对SIN感染大多具有抗性,但所测试的十个结肠癌细胞系中有九个对SIN感染敏感。此外,SIN易感性与结肠癌细胞的转移潜能相关。两种高度侵袭性的细胞系SW620和COLO-320DM对SIN感染最为敏感。同样,在结肠癌进展的小鼠异种移植模型中,SIN优先靶向转移肿瘤细胞。尽管SW620细胞中的病毒附着和进入明显增强,但较高的感染率并非由于SIN感染的特异性受体67kD层粘连蛋白受体表达增加所致。这些结果表明,SIN在感染过程中可能采用了一种新的细胞附着/进入机制,从而能够选择性地靶向结肠癌细胞。