Journal
JOURNAL OF CLINICAL INVESTIGATION
Volume 117, Issue 5, Pages 1305-1313Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI30740
Keywords
-
Categories
Funding
- NCI NIH HHS [P50 CA 98131, R01 CA062212, R01 CA 85492, P30 CA 68485, R01 CA038079, R01 CA102162, P50 CA098131, R01 CA085492, P30 CA068485, R01 CA 38079, R01 CA 102162, R01 CA 62212] Funding Source: Medline
Ask authors/readers for more resources
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-beta 1 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 prometastatic signal in tumor cells and provide a rationale for the simultaneous use of these therapies in combination with TGF-beta inhibitors.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available