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

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 ci...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of clinical investigation 2007-05, Vol.117 (5), p.1305
Main Authors: Biswas, Swati, Guix, Marta, Rinehart, Cammie, Dugger, Teresa C
Format: Article
Language:English
Subjects:
Antibodies
Antigens
Apoptosis
Biomedical research
Breast cancer
Cancer therapies
Cell cycle
Chemotherapy
Ligands
Lungs
Metastasis
Plasma
Radiation
Thorax
Transgenic animals
Tumors
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0021-9738
1558-8238