Expression of the B-cell receptor component CD79a on immature myeloid cells contributes to their tumor promoting effects.
The role of myeloid derived suppressor cells (MDSCs) in promoting tumorigenesis is well-established, and significant effort is being made to further characterize surface markers on MDSCs both for better diagnosis and as potential targets for therapy. Here we show that the B cell receptor adaptor mol...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0076115 |
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| author | Dror Luger Yu-An Yang Asaf Raviv Douglas Weinberg Subhadra Banerjee Min-Jung Lee Jane Trepel Li Yang Lalage M Wakefield |
| author_facet | Dror Luger Yu-An Yang Asaf Raviv Douglas Weinberg Subhadra Banerjee Min-Jung Lee Jane Trepel Li Yang Lalage M Wakefield |
| author_sort | Dror Luger |
| collection | DOAJ |
| description | The role of myeloid derived suppressor cells (MDSCs) in promoting tumorigenesis is well-established, and significant effort is being made to further characterize surface markers on MDSCs both for better diagnosis and as potential targets for therapy. Here we show that the B cell receptor adaptor molecule CD79a is unexpectedly expressed on immature bone marrow myeloid cells, and is upregulated on MDSCs generated in multiple different mouse models of metastatic but not non-metastatic cancer. CD79a on MDSCs is upregulated and activated in response to soluble factors secreted by tumor cells. Activation of CD79a on mouse MDSCs, by crosslinking with a specific antibody, maintained their immature phenotype (CD11b+Gr1+), enhanced their migration, increased their suppressive effect on T cell proliferation, and increased secretion of pro-tumorigenic cytokines such as IL-6 and CCL22. Furthermore, crosslinking CD79a on myeloid cells activated signaling through Syk, BLNK, ERK and STAT3 phosphorylation. In vivo, CD79+ myeloid cells showed enhanced ability to promote primary tumor growth and metastasis. Finally we demonstrate that CD79a is upregulated on circulating myeloid cells from lung cancer patients, and that CD79a+ myeloid cells infiltrate human breast tumors. We propose that CD79a plays a functional role in the tumor promoting effects of myeloid cells, and may represent a novel target for cancer therapy. |
| format | Article |
| id | doaj-art-de4481643bb24dd5ba45ae650e71833e |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-de4481643bb24dd5ba45ae650e71833e2025-08-20T02:33:11ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01810e7611510.1371/journal.pone.0076115Expression of the B-cell receptor component CD79a on immature myeloid cells contributes to their tumor promoting effects.Dror LugerYu-An YangAsaf RavivDouglas WeinbergSubhadra BanerjeeMin-Jung LeeJane TrepelLi YangLalage M WakefieldThe role of myeloid derived suppressor cells (MDSCs) in promoting tumorigenesis is well-established, and significant effort is being made to further characterize surface markers on MDSCs both for better diagnosis and as potential targets for therapy. Here we show that the B cell receptor adaptor molecule CD79a is unexpectedly expressed on immature bone marrow myeloid cells, and is upregulated on MDSCs generated in multiple different mouse models of metastatic but not non-metastatic cancer. CD79a on MDSCs is upregulated and activated in response to soluble factors secreted by tumor cells. Activation of CD79a on mouse MDSCs, by crosslinking with a specific antibody, maintained their immature phenotype (CD11b+Gr1+), enhanced their migration, increased their suppressive effect on T cell proliferation, and increased secretion of pro-tumorigenic cytokines such as IL-6 and CCL22. Furthermore, crosslinking CD79a on myeloid cells activated signaling through Syk, BLNK, ERK and STAT3 phosphorylation. In vivo, CD79+ myeloid cells showed enhanced ability to promote primary tumor growth and metastasis. Finally we demonstrate that CD79a is upregulated on circulating myeloid cells from lung cancer patients, and that CD79a+ myeloid cells infiltrate human breast tumors. We propose that CD79a plays a functional role in the tumor promoting effects of myeloid cells, and may represent a novel target for cancer therapy.https://doi.org/10.1371/journal.pone.0076115 |
| spellingShingle | Dror Luger Yu-An Yang Asaf Raviv Douglas Weinberg Subhadra Banerjee Min-Jung Lee Jane Trepel Li Yang Lalage M Wakefield Expression of the B-cell receptor component CD79a on immature myeloid cells contributes to their tumor promoting effects. PLoS ONE |
| title | Expression of the B-cell receptor component CD79a on immature myeloid cells contributes to their tumor promoting effects. |
| title_full | Expression of the B-cell receptor component CD79a on immature myeloid cells contributes to their tumor promoting effects. |
| title_fullStr | Expression of the B-cell receptor component CD79a on immature myeloid cells contributes to their tumor promoting effects. |
| title_full_unstemmed | Expression of the B-cell receptor component CD79a on immature myeloid cells contributes to their tumor promoting effects. |
| title_short | Expression of the B-cell receptor component CD79a on immature myeloid cells contributes to their tumor promoting effects. |
| title_sort | expression of the b cell receptor component cd79a on immature myeloid cells contributes to their tumor promoting effects |
| url | https://doi.org/10.1371/journal.pone.0076115 |
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