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TGF-β signaling in myeloid cells is required for tumor metastasis.
|Title||TGF-β signaling in myeloid cells is required for tumor metastasis.|
|Publication Type||Journal Article|
|Year of Publication||2013|
|Authors||Pang Y, Gara SK, Achyut BR, Li Z, Yan HH, Day C-P, Weiss JM, Trinchieri G, Morris JC, Yang L|
|Date Published||2013 Aug|
TGF-β is overexpressed in advanced human cancers. It correlates with metastasis and poor prognosis. However, TGF-β 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-β1, arginase 1, and inducible nitric oxide synthase, which promoted IFN-γ 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-β receptor II expression. Our studies show that myeloid-specific TGF-β signaling is an essential component of the metastasis-promoting puzzle of TGF-β. This is in contrast to the previously reported tumor-suppressing phenotypes in fibroblasts, epithelial cells, and T cells.
|Alternate Journal||Cancer Discov|