Rebecca Cook
Faculty Member
Last active: 4/15/2019

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

Muraoka RS, Dumont N, Ritter CA, Dugger TC, Brantley DM, Chen J, Easterly E, Roebuck LR, Ryan S, Gotwals PJ, Koteliansky V, Arteaga CL
J Clin Invest. 2002 109 (12): 1551-9

PMID: 12070302 · PMCID: PMC151012 · DOI:10.1172/JCI15234

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.

MeSH Terms (28)

Animals Antigens, Polyomavirus Transforming Apoptosis Autocrine Communication Breast Cell Movement Cell Survival Female Genetic Vectors Immunoglobulin Fc Fragments Immunoglobulin G Lung Neoplasms Mammary Neoplasms, Animal Mammary Tumor Virus, Mouse Mice Mice, Inbred BALB C Mice, Transgenic Neoplasm Metastasis Neovascularization, Pathologic Protein-Serine-Threonine Kinases Receptor, Transforming Growth Factor-beta Type II Receptors, Transforming Growth Factor beta Recombinant Fusion Proteins Signal Transduction Solubility Transforming Growth Factor beta Transforming Growth Factor beta1 Tumor Cells, Cultured

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