A soluble transforming growth factor beta type III receptor suppresses tumorigenicity and metastasis of human breast cancer MDA-MB-231 cells.
Transforming growth factor beta (TGF-beta) can promote late stage tumor progression in a number of model systems. In the present study, we have examined whether expression of a truncated soluble extracellular domain of TGF-beta type III receptor (sRIII) in human breast cancer MDA-MB-231 cells can antagonize the tumor-promoting activity of TGF-beta by sequestering active TGF-beta isoforms that are produced by the cancer cells. The secretion of sRIII reduced the amount of active TGF-beta1 and TGF-beta2 in the conditioned medium. This led to a significant reduction of the growth-inhibitory activity of the medium conditioned by sRIII-expressing cells on the growth of mink lung epithelial CCL64 cells in comparison with the medium conditioned by the control cells. The tumor incidence and growth rate of all of the three sRIII-expressing clones studied were significantly lower than those of the control cells in athymic nude mice. Four of five control cell-inoculated mice showed spontaneous metastasis in the lung, whereas none of the sRIII-expressing cell-inoculated mice had any lung metastasis. Thus, our results suggest that the sRIII may be used to antagonize the tumor-promoting activity of TGF-beta.
Bandyopadhyay
A
A
Department of Pharmacology, University of Kentucky College of Medicine, Lexington 40536, USA.
Zhu
Y
Y
Cibull
M L
ML
Bao
L
L
Chen
C
C
Sun
L
L
D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology*; D002460:Cell Line; D017077:Culture Media, Conditioned; D005260:Female; D006801:Humans; D008168:Lung; D008175:Lung Neoplasms / Q000473:pathology / Q000517:prevention & control / Q000556:secondary*; D051379:Mice; D008819:Mice, Nude; D008907:Mink; D009362:Neoplasm Metastasis; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000502:physiology*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D017077:Culture Media, Conditioned; D018125:Receptors, Transforming Growth Factor beta; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II