Department of Biochemistry, University of Alberta, Edmonton, AB T6G 2S2, Canada.
Cancer Research Institute of Northern Alberta, University of Alberta, Edmonton, AB T6G 2S2, Canada.
Int J Mol Sci. 2021 Sep 10;22(18):9817. doi: 10.3390/ijms22189817.
Human cytomegalovirus (HCMV) infects 40-70% of adults in developed countries. HCMV proteins and DNA are detected in tumors and metastases, suggesting an association with increased invasion. We investigated HCMV infection in human breast cancer cell lines compared to fibroblasts, a component of tumors, and the role of platelet-derived growth factor receptor-α (PDGFRα). HCMV productively infected HEL299 fibroblasts and, to a lesser extent, Hs578T breast cancer cells. Infection of another triple-negative cell line, MDA-MB-231, and also MCF-7 cells, was extremely low. These disparate infection rates correlated with expression of , which facilitates HCMV uptake. Increasing expression in T-47D breast cancer and BCPAP thyroid cancer cells markedly increased HCMV infection. Conversely, HCMV infection decreased expression, potentially attenuating signaling through this receptor. HCMV infection of fibroblasts promoted the secretion of proinflammatory factors, whereas an overall decreased secretion of inflammatory factors was observed in infected Hs578T cells. We conclude that HCMV infection in tumors will preferentially target tumor-associated fibroblasts and breast cancer cells expressing PDGFRα. HCMV infection in the tumor microenvironment, rather than cancer cells, will increase the inflammatory milieu that could enhance metastasis involving lysophosphatidate.
人巨细胞病毒（HCMV）感染发达国家 40-70%的成年人。HCMV 蛋白和 DNA 在肿瘤和转移灶中被检测到，这表明其与侵袭增加有关。我们研究了人乳腺癌细胞系与成纤维细胞（肿瘤的组成部分）中 HCMV 感染的情况，以及血小板衍生生长因子受体-α（PDGFRα）的作用。HCMV 可有效地感染 HEL299 成纤维细胞，在较小程度上也可感染 Hs578T 乳腺癌细胞。另一种三阴性细胞系 MDA-MB-231 和 MCF-7 细胞的感染率极低。这些不同的感染率与 的表达相关，这有利于 HCMV 的摄取。在 T-47D 乳腺癌和 BCPAP 甲状腺癌细胞中增加 的表达显著增加了 HCMV 的感染。相反，HCMV 感染降低了 的表达，可能通过该受体减弱信号转导。成纤维细胞中 HCMV 的感染促进促炎因子的分泌，而在受感染的 Hs578T 细胞中观察到促炎因子的总体分泌减少。我们得出结论，肿瘤中的 HCMV 感染将优先靶向肿瘤相关成纤维细胞和表达 PDGFRα 的乳腺癌细胞。肿瘤微环境中的 HCMV 感染而不是癌细胞，将增加炎症环境，这可能会增强涉及溶血磷脂酸的转移。
