{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:19:56Z","timestamp":1760235596871,"version":"build-2065373602"},"reference-count":51,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2021,9,10]],"date-time":"2021-09-10T00:00:00Z","timestamp":1631232000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000015","name":"Canadian Cancer Society Research Institute","doi-asserted-by":"publisher","award":["300034"],"award-info":[{"award-number":["300034"]}],"id":[{"id":"10.13039\/501100000015","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010090","name":"Women and Children's Health Research Institute","doi-asserted-by":"publisher","award":["01"],"award-info":[{"award-number":["01"]}],"id":[{"id":"10.13039\/100010090","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MOP123488","PJT-169140"],"award-info":[{"award-number":["MOP123488","PJT-169140"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Li Ka Shing Institute of Virology, University of Alberta","award":["DG Hemmings"],"award-info":[{"award-number":["DG Hemmings"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Human cytomegalovirus (HCMV) infects 40\u201370% 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-\u03b1 (PDGFR\u03b1). 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 PDGFRA, which facilitates HCMV uptake. Increasing PDGFRA expression in T-47D breast cancer and BCPAP thyroid cancer cells markedly increased HCMV infection. Conversely, HCMV infection decreased PDGFRA 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 PDGFR\u03b1. HCMV infection in the tumor microenvironment, rather than cancer cells, will increase the inflammatory milieu that could enhance metastasis involving lysophosphatidate.<\/jats:p>","DOI":"10.3390\/ijms22189817","type":"journal-article","created":{"date-parts":[[2021,9,10]],"date-time":"2021-09-10T10:31:34Z","timestamp":1631269894000},"page":"9817","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["PDGFR\u03b1 Enhanced Infection of Breast Cancer Cells with Human Cytomegalovirus but Infection of Fibroblasts Increased Prometastatic Inflammation Involving Lysophosphatidate Signaling"],"prefix":"10.3390","volume":"22","author":[{"given":"Zelei","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Biochemistry, University of Alberta, Edmonton, AB T6G 2S2, Canada"},{"name":"Cancer Research Institute of Northern Alberta, University of Alberta, Edmonton, AB T6G 2S2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyun","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Alberta, Edmonton, AB T6G 2S2, Canada"},{"name":"Cancer Research Institute of Northern Alberta, University of Alberta, Edmonton, AB T6G 2S2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Todd P. W.","family":"McMullen","sequence":"additional","affiliation":[{"name":"Cancer Research Institute of Northern Alberta, University of Alberta, Edmonton, AB T6G 2S2, Canada"},{"name":"Department of Surgery, University of Alberta, Edmonton, AB T6G 2B7, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2227-0020","authenticated-orcid":false,"given":"David N.","family":"Brindley","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Alberta, Edmonton, AB T6G 2S2, Canada"},{"name":"Cancer Research Institute of Northern Alberta, University of Alberta, Edmonton, AB T6G 2S2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denise G.","family":"Hemmings","sequence":"additional","affiliation":[{"name":"Cancer Research Institute of Northern Alberta, University of Alberta, Edmonton, AB T6G 2S2, Canada"},{"name":"Cardiovascular Research Center, Medical Microbiology and Immunology, Obstetrics and Gynecology, Women and Children\u2019s Health Research Institute, Li Ka Shing Institute of Virology, University of Alberta, Edmonton, AB T6G 2S2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e609","DOI":"10.1016\/S2214-109X(16)30143-7","article-title":"Global burden of cancers attributable to infections in 2012: A synthetic analysis","volume":"4","author":"Plummer","year":"2016","journal-title":"Lancet Glob. 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