| First Author | Muraoka RS | Year | 2002 |
| Journal | J Clin Invest | Volume | 109 |
| Issue | 12 | Pages | 1551-9 |
| PubMed ID | 12070302 | Mgi Jnum | J:86709 |
| Mgi Id | MGI:2681360 | Doi | 10.1172/JCI15234 |
| Citation | Muraoka RS, et al. (2002) Blockade of TGF-beta inhibits mammary tumor cell viability, migration, and metastases. J Clin Invest 109(12):1551-9 |
| abstractText | 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. |
