T cell- but not tumor cell-produced TGF-β1 promotes the development of spontaneous mammary cancer

• Published in: Oncotarget 2011-12, Vol.2 (12), p.1339-1351
• Main Authors: Sarkar, Abira, Donkor, Moses K, Li, Ming O
• Format: Article
• Language: English
• Subjects: Animals; Female; Mammary Neoplasms, Animal - metabolism; Mammary Neoplasms, Animal - pathology; Mammary Neoplasms, Experimental - metabolism; Mammary Neoplasms, Experimental - pathology; Mice; Mice, Inbred C57BL; Mice, Knockout; Research s; T-Lymphocytes - metabolism; Transforming Growth Factor beta - genetics; Transforming Growth Factor beta - metabolism
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.403

During their development, tumors acquire multiple capabilities that enable them to proliferate, disseminate and evade immunosurveillance. A putative mechanism is through the production of the cytokine TGF-β1. We showed in our recent studies that T cell-produced TGF-β1 inhibits antitumor T cell responses to foster tumor growth raising the question of the precise function of TGF-β1 produced by tumor cells in tumor development. Here, using a transgenic model of mammary cancer, we report that deletion of TGF-β1 from tumor cells did not protect mice from tumor development. However, ablation of TGF-β1 from T cells significantly inhibited mammary tumor growth. Additionally, absence of TGF-β1 in T cells prevented tumors from advancing to higher pathological grades and further suppressed secondary tumor development in the lungs. These findings reveal T cells but not tumor cells as a critical source of TGF-β1 that promotes tumor development.