TGF-β signaling in myeloid cells is required for tumor metastasis.

TitleTGF-β signaling in myeloid cells is required for tumor metastasis.
Publication TypeJournal Article
Year of Publication2013
AuthorsPang Y, Gara SK, Achyut BR, Li Z, Yan HH, Day C-P, Weiss JM, Trinchieri G, Morris JC, Yang L
JournalCancer discovery
Volume3
Issue8
Pagination936-51
Date Published2013 Aug
Abstract

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.

DOI10.3980/j.issn.2222-3959.2013.03.08
Alternate JournalCancer Discov