An expanded myeloid derived suppressor cell population does not play a role in gammaherpesvirus-exacerbated breast cancer metastases
<p>Abstract</p> <p>Background</p> <p>Mice latently infected with murine gammaherpesvirus 68 (HV-68) and transplanted with 4 T1 breast cancer cells developed exacerbated metastatic lesions when compared to controls. The mechanisms responsible for this viral-exacerbated d...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2012-09-01
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| Series: | Infectious Agents and Cancer |
| Subjects: | |
| Online Access: | http://www.infectagentscancer.com/content/7/1/22 |
| _version_ | 1818662888052621312 |
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| author | Nelson Daniel A Chauhan Vinita S Tolbert Melanie D Bost Kenneth L |
| author_facet | Nelson Daniel A Chauhan Vinita S Tolbert Melanie D Bost Kenneth L |
| author_sort | Nelson Daniel A |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Mice latently infected with murine gammaherpesvirus 68 (HV-68) and transplanted with 4 T1 breast cancer cells developed exacerbated metastatic lesions when compared to controls. The mechanisms responsible for this viral-exacerbated disease were not clear. The ability of HV-68 infection to induce S100A8 and S100A9 production and to expand a population of CD11b+Gr-1+ cells suggested that increased numbers, or activity, of viral-expanded myeloid derived suppressor cells (MDSCs) might contribute to HV-68-associated metastatic breast cancer in this model. We questioned whether mock or HV-68 infected mice with significant breast cancer might have differences in the number and/or activity of MDSCs.</p> <p>Methods</p> <p>Myeloid-derived macrophages and dendritic cells were isolated from normal mice and cultured in vitro with HV-68 to assess S100A8 and S100A9 mRNA and protein expression. In vivo studies were performed using groups of mice that were mock treated or infected with HV-68. After viral latency was established, 4 T1 breast cancer cells were transplanted in mice. When primary breast tumors were present mice were euthanized and cells isolated for phenotyping of myeloid cell populations using FACS, and for ex vivo analysis of suppressor activity. Serum from these animals was also collected to quantify S100A8 and S100A9 levels.</p> <p>Results</p> <p>In vitro studies demonstrated that direct exposure of myeloid cells to HV-68 did not induce increased expression of S100A8 or S100A9 mRNAs or secreted protein. HV-68 infected mice with metastatic breast cancer disease had no increases in S100A8/A9 levels and no significant increases in the numbers or activation of CD11b+Gr-1+MDSCs when compared to mock treated mice with breast cancer.</p> <p>Conclusions</p> <p>Together these studies are consistent with the notion that expanded myeloid derived suppressor cells do not play a role in gammaherpesvirus-exacerbated breast cancer metastases. The mechanisms responsible for HV-68 induced exacerbation of metastatic breast cancer remain unclear.</p> |
| first_indexed | 2024-12-17T05:08:06Z |
| format | Article |
| id | doaj.art-9d6ed6ae0cb9469da136c0198a27c124 |
| institution | Directory Open Access Journal |
| issn | 1750-9378 |
| language | English |
| last_indexed | 2024-12-17T05:08:06Z |
| publishDate | 2012-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Infectious Agents and Cancer |
| spelling | doaj.art-9d6ed6ae0cb9469da136c0198a27c1242022-12-21T22:02:21ZengBMCInfectious Agents and Cancer1750-93782012-09-01712210.1186/1750-9378-7-22An expanded myeloid derived suppressor cell population does not play a role in gammaherpesvirus-exacerbated breast cancer metastasesNelson Daniel AChauhan Vinita STolbert Melanie DBost Kenneth L<p>Abstract</p> <p>Background</p> <p>Mice latently infected with murine gammaherpesvirus 68 (HV-68) and transplanted with 4 T1 breast cancer cells developed exacerbated metastatic lesions when compared to controls. The mechanisms responsible for this viral-exacerbated disease were not clear. The ability of HV-68 infection to induce S100A8 and S100A9 production and to expand a population of CD11b+Gr-1+ cells suggested that increased numbers, or activity, of viral-expanded myeloid derived suppressor cells (MDSCs) might contribute to HV-68-associated metastatic breast cancer in this model. We questioned whether mock or HV-68 infected mice with significant breast cancer might have differences in the number and/or activity of MDSCs.</p> <p>Methods</p> <p>Myeloid-derived macrophages and dendritic cells were isolated from normal mice and cultured in vitro with HV-68 to assess S100A8 and S100A9 mRNA and protein expression. In vivo studies were performed using groups of mice that were mock treated or infected with HV-68. After viral latency was established, 4 T1 breast cancer cells were transplanted in mice. When primary breast tumors were present mice were euthanized and cells isolated for phenotyping of myeloid cell populations using FACS, and for ex vivo analysis of suppressor activity. Serum from these animals was also collected to quantify S100A8 and S100A9 levels.</p> <p>Results</p> <p>In vitro studies demonstrated that direct exposure of myeloid cells to HV-68 did not induce increased expression of S100A8 or S100A9 mRNAs or secreted protein. HV-68 infected mice with metastatic breast cancer disease had no increases in S100A8/A9 levels and no significant increases in the numbers or activation of CD11b+Gr-1+MDSCs when compared to mock treated mice with breast cancer.</p> <p>Conclusions</p> <p>Together these studies are consistent with the notion that expanded myeloid derived suppressor cells do not play a role in gammaherpesvirus-exacerbated breast cancer metastases. The mechanisms responsible for HV-68 induced exacerbation of metastatic breast cancer remain unclear.</p>http://www.infectagentscancer.com/content/7/1/22Myeloid derived suppressor cellsGammaherpesvirusBreast cancer |
| spellingShingle | Nelson Daniel A Chauhan Vinita S Tolbert Melanie D Bost Kenneth L An expanded myeloid derived suppressor cell population does not play a role in gammaherpesvirus-exacerbated breast cancer metastases Infectious Agents and Cancer Myeloid derived suppressor cells Gammaherpesvirus Breast cancer |
| title | An expanded myeloid derived suppressor cell population does not play a role in gammaherpesvirus-exacerbated breast cancer metastases |
| title_full | An expanded myeloid derived suppressor cell population does not play a role in gammaherpesvirus-exacerbated breast cancer metastases |
| title_fullStr | An expanded myeloid derived suppressor cell population does not play a role in gammaherpesvirus-exacerbated breast cancer metastases |
| title_full_unstemmed | An expanded myeloid derived suppressor cell population does not play a role in gammaherpesvirus-exacerbated breast cancer metastases |
| title_short | An expanded myeloid derived suppressor cell population does not play a role in gammaherpesvirus-exacerbated breast cancer metastases |
| title_sort | expanded myeloid derived suppressor cell population does not play a role in gammaherpesvirus exacerbated breast cancer metastases |
| topic | Myeloid derived suppressor cells Gammaherpesvirus Breast cancer |
| url | http://www.infectagentscancer.com/content/7/1/22 |
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