| First Author | Sahoo M | Year | 2018 |
| Journal | Oncotarget | Volume | 9 |
| Issue | 69 | Pages | 33215-33231 |
| PubMed ID | 30237863 | Mgi Jnum | J:274048 |
| Mgi Id | MGI:6295721 | Doi | 10.18632/oncotarget.26061 |
| Citation | Sahoo M, et al. (2018) Hematopoietic stem cell specific V-ATPase controls breast cancer progression and metastasis via cytotoxic T cells. Oncotarget 9(69):33215-33231 |
| abstractText | The interaction of recruited immune effector cells and cancer cells within tumor microenvironment (TME) shapes the fate of cancer progression and metastasis. Many cancers including breast cancer, express a specific vacuolar ATPase (a2V) on their cell surface which acidifies the extracellular milieu helping cancer cell proliferation and metastasis. To understand the role of immune cell-associated-a2V during breast tumor pathogenesis, we knocked-out a2V (KO) from the hematopoietic stem cells (HSC) and generated breast tumors in mice. The a2V-KO mice developed faster growing, larger, and metastatic breast tumors compared to control mice. Further investigation of the TME revealed a significant reduction in the presence of CD4(+) and CD8(+) T cells in the a2V-KO tumors. Targeted RNA-Seq of the cells of the TME demonstrated that pro-inflammatory cytokines, death receptors, death receptor ligands, and cytotoxic effectors were significantly down-regulated within the a2V-KO TME. Interestingly, analysis of immune cells in the blood, spleen, and thymus of the non-tumor bearing a2V-KO mice revealed a significant decrease in CD4(+) and CD8(+) T cell populations. For the first time, this study demonstrates that inhibition of V-ATPase expression in HSC leads to a decrease in CD4(+) and CD8(+) T cell populations and thus promotes breast tumor growth and metastasis. |
