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

J Clin Invest. 2007 May;117(5):1305-13. doi: 10.1172/JCI30740. Epub 2007 Apr 5.


We investigated whether TGF-beta 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-beta1 as well as increased circulating tumor cells and lung metastases. These effects were abrogated by administration of a neutralizing pan-TGF-beta antibody. Circulating polyomavirus middle T antigen-expressing tumor cells did not grow ex vivo in the presence of the TGF-beta antibody, suggesting autocrine TGF-beta is a survival signal in these cells. Radiation failed to enhance lung metastases in mice bearing tumors that lack the type II TGF-beta receptor, suggesting that the increase in metastases was due, at least in part, to a direct effect of TGF-beta on the cancer cells. These data implicate TGF-beta induced by anticancer therapy as a pro-metastatic signal in tumor cells and provide a rationale for the simultaneous use of these therapies in combination with TGF-beta inhibitors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Blocking / therapeutic use*
  • Antigens, Polyomavirus Transforming / physiology
  • Cell Line, Tumor
  • Female
  • Humans
  • Lung Neoplasms / immunology
  • Lung Neoplasms / prevention & control*
  • Lung Neoplasms / secondary*
  • Mammary Neoplasms, Experimental / immunology*
  • Mammary Neoplasms, Experimental / therapy*
  • Mammary Tumor Virus, Mouse / physiology
  • Mice
  • Mice, Transgenic
  • Neoplasms, Radiation-Induced / immunology
  • Neoplasms, Radiation-Induced / pathology
  • Neoplasms, Radiation-Induced / prevention & control*
  • Neoplastic Cells, Circulating / immunology
  • Neoplastic Cells, Circulating / pathology
  • Retroviridae Infections / pathology
  • Retroviridae Infections / prevention & control
  • Signal Transduction / physiology
  • Transforming Growth Factor beta / antagonists & inhibitors*
  • Transforming Growth Factor beta / immunology*
  • Tumor Virus Infections / pathology
  • Tumor Virus Infections / prevention & control


  • Antibodies, Blocking
  • Antigens, Polyomavirus Transforming
  • Transforming Growth Factor beta