PDGFRα Enhanced Infection of Breast Cancer Cells with Human Cytomegalovirus but Infection of Fibroblasts Increased Prometastatic Inflammation Involving Lysophosphatidate Signaling
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 tumor...
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MDPI AG
2021-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/18/9817 |
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doaj-c917711f5f9f4e8d989320ff94c5a23d2021-09-26T00:23:00ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-09-01229817981710.3390/ijms22189817PDGFRα Enhanced Infection of Breast Cancer Cells with Human Cytomegalovirus but Infection of Fibroblasts Increased Prometastatic Inflammation Involving Lysophosphatidate SignalingZelei Yang0Xiaoyun Tang1Todd P. W. McMullen2David N. Brindley3Denise G. Hemmings4Department of Biochemistry, University of Alberta, Edmonton, AB T6G 2S2, CanadaDepartment of Biochemistry, University of Alberta, Edmonton, AB T6G 2S2, CanadaCancer Research Institute of Northern Alberta, University of Alberta, Edmonton, AB T6G 2S2, CanadaDepartment of Biochemistry, University of Alberta, Edmonton, AB T6G 2S2, CanadaCancer Research Institute of Northern Alberta, University of Alberta, Edmonton, AB T6G 2S2, CanadaHuman 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 <i>PDGFRA</i>, which facilitates HCMV uptake. Increasing <i>PDGFRA</i> expression in T-47D breast cancer and BCPAP thyroid cancer cells markedly increased HCMV infection. Conversely, HCMV infection decreased <i>PDGFRA</i> 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.https://www.mdpi.com/1422-0067/22/18/9817autotaxinchemokinescytokineslipid phosphate phosphataseslysophosphatidic acid |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Zelei Yang Xiaoyun Tang Todd P. W. McMullen David N. Brindley Denise G. Hemmings |
| spellingShingle |
Zelei Yang Xiaoyun Tang Todd P. W. McMullen David N. Brindley Denise G. Hemmings PDGFRα Enhanced Infection of Breast Cancer Cells with Human Cytomegalovirus but Infection of Fibroblasts Increased Prometastatic Inflammation Involving Lysophosphatidate Signaling International Journal of Molecular Sciences autotaxin chemokines cytokines lipid phosphate phosphatases lysophosphatidic acid |
| author_facet |
Zelei Yang Xiaoyun Tang Todd P. W. McMullen David N. Brindley Denise G. Hemmings |
| author_sort |
Zelei Yang |
| title |
PDGFRα Enhanced Infection of Breast Cancer Cells with Human Cytomegalovirus but Infection of Fibroblasts Increased Prometastatic Inflammation Involving Lysophosphatidate Signaling |
| title_short |
PDGFRα Enhanced Infection of Breast Cancer Cells with Human Cytomegalovirus but Infection of Fibroblasts Increased Prometastatic Inflammation Involving Lysophosphatidate Signaling |
| title_full |
PDGFRα Enhanced Infection of Breast Cancer Cells with Human Cytomegalovirus but Infection of Fibroblasts Increased Prometastatic Inflammation Involving Lysophosphatidate Signaling |
| title_fullStr |
PDGFRα Enhanced Infection of Breast Cancer Cells with Human Cytomegalovirus but Infection of Fibroblasts Increased Prometastatic Inflammation Involving Lysophosphatidate Signaling |
| title_full_unstemmed |
PDGFRα Enhanced Infection of Breast Cancer Cells with Human Cytomegalovirus but Infection of Fibroblasts Increased Prometastatic Inflammation Involving Lysophosphatidate Signaling |
| title_sort |
pdgfrα enhanced infection of breast cancer cells with human cytomegalovirus but infection of fibroblasts increased prometastatic inflammation involving lysophosphatidate signaling |
| publisher |
MDPI AG |
| series |
International Journal of Molecular Sciences |
| issn |
1661-6596 1422-0067 |
| publishDate |
2021-09-01 |
| description |
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 <i>PDGFRA</i>, which facilitates HCMV uptake. Increasing <i>PDGFRA</i> expression in T-47D breast cancer and BCPAP thyroid cancer cells markedly increased HCMV infection. Conversely, HCMV infection decreased <i>PDGFRA</i> 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. |
| topic |
autotaxin chemokines cytokines lipid phosphate phosphatases lysophosphatidic acid |
| url |
https://www.mdpi.com/1422-0067/22/18/9817 |
| work_keys_str_mv |
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