Blockade of TGF-β inhibits mammary tumor cell viability, migration, and metastases

Rebecca S. Muraoka, 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

Research output: Contribution to journalArticle

412 Scopus citations

Abstract

TGF-βs are potent inhibitors of epithelial cell proliferation. However, in established carcinomas, autocrine/paracrine TGF-β interactions can enhance tumor cell viability and progression. Thus, we studied the effect of a soluble Fc:TGF-β type II receptor fusion protein (Fc: TβRII) on transgenic and transplantable models of breast cancer metastases. Systemic administration of Fc: TβRII did not alter primary mammary tumor latency in MMTV-Polyomavirus middle T antigen transgenic mice. However, Fc: TβRII 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: TβRII 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: TβRII. Therefore, blockade of TGF-β signaling may reduce tumor cell viability and migratory potential and represents a testable therapeutic approach against metastatic carcinomas.

Original languageEnglish (US)
Pages (from-to)1551-1559
Number of pages9
JournalJournal of Clinical Investigation
Volume109
Issue number12
DOIs
StatePublished - Jan 1 2002

ASJC Scopus subject areas

  • Medicine(all)

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    Muraoka, R. S., Dumont, N., Ritter, C. A., Dugger, T. C., Brantley, D. M., Chen, J., Easterly, E., Renee Roebuck, L., Ryan, S., Gotwals, P. J., Koteliansky, V., & Arteaga, C. L. (2002). Blockade of TGF-β inhibits mammary tumor cell viability, migration, and metastases. Journal of Clinical Investigation, 109(12), 1551-1559. https://doi.org/10.1172/JCI0215234