Soluble transforming growth factor beta type II receptor attenuates TGF-beta1 activity in human colorectal cancer LoVo cells.
Several lines of evidence support an important role of TGF-beta in the development of colorectal cancer, although the molecular consequences are largely unknown. Soluble transforming growth factor-beta receptor type II (sTbetaRII) is a target of transforming growth factors-beta (TGF-beta) that plays an important role in regulation tumorigenesis, angiogenesis and metastasis of cancer. To elucidate whether overexpression of sTbetaRII could antagonize TGF-beta in colon cancer cells, we constructed a plasmid that contains a cDNA encoding human extracellular region of TbetaRII and transfected this construction into LoVo cells. Surprisingly, in the absence of TGF-beta1, the overexpression of sTbetaRII antagonized TGF-beta-induced cell proliferation, invasion, motility and angiogenesis, and decreased expression of VEGF and MMP-9. Also, sTbetaRII inhibited TGF-beta-induced apoptosis and improved the induction of antitumor immunity. Our data indicated that sTbetaRII attenuated the biological activities of TGF-beta, suggesting that sTbetaRII may have a therapeutic benefit in colorectal cancer.
Zhou
Rui
R
Department of Oncology, Zhongnan Hospital, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Wuhan 430071, P.R. China.
Xiong
Bin
B
Song
Haibin
H
Liu
Shiquan
S
Wang
Xinbo
X
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D018076:DNA, Complementary / Q000378:metabolism; D005822:Genetic Vectors; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism / Q000502:physiology*; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism / Q000502:physiology*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
D000970:Antineoplastic Agents; D018076:DNA, Complementary; D018125:Receptors, Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II