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

RS Muraoka, N Dumont, CA Ritter… - The Journal of …, 2002 - Am Soc Clin Investig
RS Muraoka, N Dumont, CA Ritter, TC Dugger, DM Brantley, J Chen, E Easterly…
The Journal of clinical investigation, 2002Am Soc Clin Investig
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 …
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.
The Journal of Clinical Investigation