| Literature DB >> 12070302 |
Rebecca S Muraoka1, Nancy Dumont, Christoph A Ritter, Teresa C Dugger, Dana M Brantley, Jin Chen, Evangeline Easterly, L Renee Roebuck, Sarah Ryan, Philip J Gotwals, Victor Koteliansky, Carlos L Arteaga.
Abstract
TGF-betas are potent inhibitors of epithelial cell proliferation. However, in established carcinomas, autocrine/paracrine TGF-beta interactions can enhance tumor cell viability and progression. Thus, we studied the effect of a soluble Fc:TGF-beta type II receptor fusion protein (Fc:TbetaRII) on transgenic and transplantable models of breast cancer metastases. Systemic administration of Fc:TbetaRII did not alter primary mammary tumor latency in MMTV-Polyomavirus middle T antigen transgenic mice. However, Fc:TbetaRII increased apoptosis in primary tumors, while reducing tumor cell motility, intravasation, and lung metastases. These effects correlated with inhibition of Akt activity and FKHRL1 phosphorylation. Fc:TbetaRII also inhibited metastases from transplanted 4T1 and EMT-6 mammary tumors in syngeneic BALB/c mice. Tumor microvessel density in a mouse dorsal skin window chamber was unaffected by Fc:TbetaRII. Therefore, blockade of TGF-beta signaling may reduce tumor cell viability and migratory potential and represents a testable therapeutic approach against metastatic carcinomas.Entities:
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Year: 2002 PMID： 12070302 PMCID： PMC151012 DOI： 10.1172/JCI15234
Source DB: PubMed Journal: J Clin Invest ISSN： 0021-9738 Impact factor: 14.808