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

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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 - Jul 2 2002

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Cell Movement
Cell Survival
Breast Neoplasms
Neoplasm Metastasis
Neoplasms
Carcinoma
Polyomavirus Transforming Antigens
Microvessels
Transgenic Mice
Epithelial Cells
Phosphorylation
Cell Proliferation
Apoptosis
Lung
Skin
Proteins
Therapeutics

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Muraoka, R. S., Dumont, N., Ritter, C. A., Dugger, T. C., Brantley, D. M., Chen, J., ... 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/JCI200215234

Blockade of TGF-β inhibits mammary tumor cell viability, migration, and metastases. / Muraoka, Rebecca S.; Dumont, Nancy; Ritter, Christoph A.; Dugger, Teresa C.; Brantley, Dana M.; Chen, Jin; Easterly, Evangeline; Renee Roebuck, L.; Ryan, Sarah; Gotwals, Philip J.; Koteliansky, Victor; Arteaga, Carlos L.

In: Journal of Clinical Investigation, Vol. 109, No. 12, 02.07.2002, p. 1551-1559.

Research output: Contribution to journalArticle

Muraoka, RS, Dumont, N, Ritter, CA, Dugger, TC, Brantley, DM, Chen, J, Easterly, E, Renee Roebuck, L, Ryan, S, Gotwals, PJ, Koteliansky, V & Arteaga, CL 2002, 'Blockade of TGF-β inhibits mammary tumor cell viability, migration, and metastases', Journal of Clinical Investigation, vol. 109, no. 12, pp. 1551-1559. https://doi.org/10.1172/JCI200215234
Muraoka RS, Dumont N, Ritter CA, Dugger TC, Brantley DM, Chen J et al. Blockade of TGF-β inhibits mammary tumor cell viability, migration, and metastases. Journal of Clinical Investigation. 2002 Jul 2;109(12):1551-1559. https://doi.org/10.1172/JCI200215234
Muraoka, Rebecca S. ; Dumont, Nancy ; Ritter, Christoph A. ; Dugger, Teresa C. ; Brantley, Dana M. ; Chen, Jin ; Easterly, Evangeline ; Renee Roebuck, L. ; Ryan, Sarah ; Gotwals, Philip J. ; Koteliansky, Victor ; Arteaga, Carlos L. / Blockade of TGF-β inhibits mammary tumor cell viability, migration, and metastases. In: Journal of Clinical Investigation. 2002 ; Vol. 109, No. 12. pp. 1551-1559.
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