Zhang Tiantian, Suryawanshi Yogesh R, Szymczyna Blair R, Essani Karim
Laboratory of Virology, Department of Biological Sciences, Western Michigan University, Kalamazoo, MI, 49008, USA.
Department of Chemistry, Western Michigan University, Kalamazoo, MI, 49008, USA.
Med Oncol. 2017 Jul;34(7):129. doi: 10.1007/s12032-017-0988-0. Epub 2017 Jun 7.
Matrix metalloproteinases (MMPs), which are involved in degradation of extracellular matrix, are critical regulators in tumor progression, metastasis and angiogenesis. Although induction of MMPs is frequently observed during the viral infection, the effect of MMPs on viral replication varies between viruses. MMP-9, for instance, is upregulated and promotes the replication of some viruses, such as herpes simplex virus, but inhibits the replication of others. Here, we report that infection with tanapox virus (TPV) promotes the expression of MMP-9 in the melanoma cells. In addition, we show that MMP-9 exerts an anti-viral effect on TPV replication and plays a protective role in TPV-infected melanoma cells in vitro. Moreover, the neutralization of MMP-9 in melanoma cells remarkably enhances the TPV infection and leads to a significant reduction in cell survival. In summary, this study contributes to understanding of the role played by MMP-9 in TPV infectivity and provides more insights for using TPV as cancer virotherapy in future studies. Since TPV has shown substantial oncolytic efficacy in promoting melanoma tumor regression in animal models, identifying mechanisms that suppress MMP-9 expression upon TPV infection can potentially improve its use as a melanoma virotherapy.
基质金属蛋白酶（MMPs）参与细胞外基质的降解，是肿瘤进展、转移和血管生成的关键调节因子。虽然在病毒感染期间经常观察到MMPs的诱导，但MMPs对病毒复制的影响因病毒而异。例如，MMP-9被上调并促进一些病毒的复制，如单纯疱疹病毒，但抑制其他病毒的复制。在这里，我们报告坦纳痘病毒（TPV）感染促进黑色素瘤细胞中MMP-9的表达。此外，我们表明MMP-9对TPV复制具有抗病毒作用，并在体外对TPV感染的黑色素瘤细胞起到保护作用。此外，黑色素瘤细胞中MMP-9的中和显著增强TPV感染并导致细胞存活率显著降低。总之，本研究有助于理解MMP-9在TPV感染性中所起的作用，并为未来研究将TPV用作癌症病毒疗法提供更多见解。由于TPV在动物模型中已显示出在促进黑色素瘤肿瘤消退方面具有显著的溶瘤疗效，确定TPV感染后抑制MMP-9表达的机制可能会潜在地改善其作为黑色素瘤病毒疗法的应用。
