Inhibition of TGF-β with neutralizing antibodies prevents radiation-induced acceleration of metastatic cancer progression

Swati Biswas, Marta Guix, Cammie Rinehart, Teresa C. Dugger, Anna Chytil, Harold L. Moses, Michael L. Freeman, Carlos L. Arteaga

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Abstract

We investigated whether TGF-β induced by anticancer therapies accelerates tumor progression. Using the MMTV/PyVmT transgenic model of metastatic breast cancer, we show that administration of ionizing radiation or doxorubicin caused increased circulating levels of TGF-β1 as well as increased circulating tumor cells and lung metastases. These effects were abrogated by administration of a neutralizing pan-TGF-β antibody. Circulating polyomavirus middle T antigen-expressing tumor cells did not grow ex vivo in the presence of the TGF-β antibody, suggesting autocrine TGF-β is a survival signal in these cells. Radiation failed to enhance lung metastases in mice bearing tumors that lack the type II TGF-β receptor, suggesting that the increase in metastases was due, at least in part, to a direct effect of TGF-β on the cancer cells. These data implicate TGF-β induced by anticancer therapy as a prometastatic signal in tumor cells and provide a rationale for the simultaneous use of these therapies in combination with TGF-β inhibitors.

Original languageEnglish (US)
Pages (from-to)1305-1313
Number of pages9
JournalJournal of Clinical Investigation
Volume117
Issue number5
DOIs
StatePublished - May 1 2007

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Neutralizing Antibodies
Radiation
Neoplasms
Neoplasm Metastasis
Polyomavirus Transforming Antigens
Circulating Neoplastic Cells
Lung
Antibodies
Ionizing Radiation
Doxorubicin
Therapeutics
Breast Neoplasms

ASJC Scopus subject areas

  • Medicine(all)

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Inhibition of TGF-β with neutralizing antibodies prevents radiation-induced acceleration of metastatic cancer progression. / Biswas, Swati; Guix, Marta; Rinehart, Cammie; Dugger, Teresa C.; Chytil, Anna; Moses, Harold L.; Freeman, Michael L.; Arteaga, Carlos L.

In: Journal of Clinical Investigation, Vol. 117, No. 5, 01.05.2007, p. 1305-1313.

Research output: Contribution to journalArticle

Biswas, Swati ; Guix, Marta ; Rinehart, Cammie ; Dugger, Teresa C. ; Chytil, Anna ; Moses, Harold L. ; Freeman, Michael L. ; Arteaga, Carlos L. / Inhibition of TGF-β with neutralizing antibodies prevents radiation-induced acceleration of metastatic cancer progression. In: Journal of Clinical Investigation. 2007 ; Vol. 117, No. 5. pp. 1305-1313.
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