Universidad Nacional de Colombia, Faculty of Medicine, Department of Physiological Sciences, Bogota, D.C., Colombia. Universidad Nacional de Colombia Universidad Nacional de Colombia Faculty of Medicine Department of Physiological Sciences Bogota Colombia.
Colomb Med (Cali). 2021 Mar 16;52(1):e2024196. doi: 10.25100/cm.v51i4.4196.
Viruses are being used as alternative and complementary tools for treating cancers. Oncolytic viruses exhibit tumor tropism, ability to enhance anti-tumor immunity and ability to be used in combination with conventional chemotherapy and radiotherapy. We have recently selected some rotavirus isolates which are adapted to efficiently infect and kill tumor cell lines.
We tested five tumor cell-adapted rotavirus isolates for their ability to infect the human adenocarcinoma cell line MCF-7.
Cell surface membrane-associated proteins mediating virus particle attachment were characterized using ELISA, immunoprecipitation, FACS analysis, and antibody blocking.
It was found that heat shock proteins (HSPs) such as Hsp90, Hsp70, Hsp60, and Hsp40 are expressed on the cell surface forming complexes with protein disulfide isomerase (PDI), integrin β3, and heat shock cognate protein 70 (Hsc70) in lipid raft microdomains. Interaction of rotavirus isolates with these cellular proteins was further confirmed by a competition assay and an inhibition assay involving the HSPs tested.
Our findings suggest that the tumor cell-adapted rotavirus isolates studied here offer a promising tool for killing tumor cells, thus encouraging further research into this topic, including animal models.
病毒正被用作治疗癌症的替代和补充工具。溶瘤病毒具有肿瘤趋向性、增强抗肿瘤免疫的能力以及与传统化疗和放疗联合应用的能力。我们最近选择了一些能够有效感染和杀死肿瘤细胞系的适应病毒株。
我们测试了 5 种肿瘤细胞适应的轮状病毒分离株,以评估它们感染人腺癌 MCF-7 细胞系的能力。
采用 ELISA、免疫沉淀、流式细胞分析和抗体阻断等方法,对介导病毒颗粒附着的细胞表面膜相关蛋白进行了表征。
发现热休克蛋白(HSPs)如 Hsp90、Hsp70、Hsp60 和 Hsp40 表达在细胞表面,与蛋白二硫键异构酶(PDI)、整合素 β3 和热休克同源蛋白 70(Hsc70)在脂筏微区形成复合物。通过竞争实验和涉及所测试 HSP 的抑制实验进一步证实了轮状病毒分离株与这些细胞蛋白的相互作用。
我们的研究结果表明,本研究中研究的肿瘤细胞适应的轮状病毒分离株为杀伤肿瘤细胞提供了一种有前途的工具,从而鼓励进一步研究这一课题,包括动物模型。