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PDGFRα Enhanced Infection of Breast Cancer Cells with Human Cytomegalovirus but Infection of Fibroblasts Increased Prometastatic Inflammation Involving Lysophosphatidate Signaling. | LitMetric

AI Article Synopsis

  • Human cytomegalovirus (HCMV) is found in 40-70% of adults in developed countries and is linked to increased tumor invasion, particularly in breast cancer.
  • In experiments, HCMV infected fibroblasts (HEL299) more effectively than breast cancer cells (e.g., Hs578T, MDA-MB-231), with infection rates tied to the expression of platelet-derived growth factor receptor-α (PDGFRα).
  • HCMV infection in fibroblasts boosted proinflammatory factor secretion, while breast cancer cells showed reduced inflammatory factors, suggesting that HCMV might enhance the tumor environment and contribute to cancer progression.

Article Abstract

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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8471290PMC
http://dx.doi.org/10.3390/ijms22189817DOI Listing

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