For several types of cancer, persistently high levels of the soluble factor TGF-beta in the blood after surgery, chemotherapy, or radiation therapy correlate with increased risk of early metastasis and a poor prognosis. Using a mouse model of breast cancer, researchers from Vanderbilt University have now generated evidence to suggest that treatment with TGF-beta inhibitors might help such patients.
In the study, which appears online on April 5 in advance of publication in the May print issue of the Journal of Clinical Investigation, Carlos Arteaga and colleagues show that treating mice with mammary tumors with either radiation or the chemotherapeutic drug doxorubicin increased the level of TGF-beta in their blood, the number of cancer cells in their blood, and the development of lung metastases. Treatment with an inhibitor of TGF-beta blocked the increased lung metastases. Furthermore, mice whose tumors did not express the receptor for TGF-beta did not develop increased incidence of lung metastases after treatment with radiation, indicating that TGF-beta affects the cancer cells directly, enhancing their metastatic function. This study has important clinical implications as it suggests that monitoring TGF-beta levels after primary therapy might indicate the patients most at risk of developing tumor metastases and that treatment with TGF-beta inhibitors might be of clinical benefit to these individuals.
TITLE: Inhibition of TGF-beta with neutralizing antibodies prevents radiation-induced acceleration of metastatic cancer progression
AUTHOR CONTACT:
Carlos L. Arteaga
Vanderbilt University School of Medicine, Nashville, Tennessee, USA
Phone: (615) 936-3524; Fax: (615) 936-1790; E-mail: carlos.arteaga@vanderbilt.edu.
View the PDF of this article at: https://www.the-jci.org/article.php?id=30740
Journal
Journal of Clinical Investigation