| First Author | Pang Y | Year | 2013 |
| Journal | Cancer Discov | Volume | 3 |
| Issue | 8 | Pages | 936-51 |
| PubMed ID | 23661553 | Mgi Jnum | J:203558 |
| Mgi Id | MGI:5527471 | Doi | 10.1158/2159-8290.CD-12-0527 |
| Citation | Pang Y, et al. (2013) TGF-beta signaling in myeloid cells is required for tumor metastasis. Cancer Discov 3(8):936-51 |
| abstractText | TGF-beta is overexpressed in advanced human cancers. It correlates with metastasis and poor prognosis. However, TGF-beta functions as both a tumor suppressor and a tumor promoter. Here, we report for the first time that genetic deletion of Tgfbr2 specifically in myeloid cells (Tgfbr2(MyeKO)) significantly inhibited tumor metastasis. Reconstitution of tumor-bearing mice with Tgfbr2(MyeKO) bone marrow recapitulated the inhibited metastasis phenotype. This effect is mediated through decreased production of type II cytokines, TGF-beta1, arginase 1, and inducible nitric oxide synthase, which promoted IFN-gamma production and improved systemic immunity. Depletion of CD8 T cells diminished the metastasis defect in the Tgfbr2(MyeKO) mice. Consistent with animal studies, myeloid cells from patients with advanced-stage cancer showed increased TGF-beta receptor II expression. Our studies show that myeloid-specific TGF-beta signaling is an essential component of the metastasis-promoting puzzle of TGF-beta. This is in contrast to the previously reported tumor-suppressing phenotypes in fibroblasts, epithelial cells, and T cells. |
