Suppression of in vivo tumorigenicity of rat hepatoma cell line KDH-8 cells by soluble TGF-beta receptor type II.
We have previously reported that transforming growth factor beta (TGF-beta) produced by rat hepatoma cell line KDH-8 cells suppressed the interleukin-2 (IL-2) production of T cells and the tumoricidal activity of macrophages in KDH-8 tumor-bearing rats and that the inhibition of TGF-beta production by low-dose bleomycin restored these activities significantly. In this study, we established three transfectant clones with stable expression of soluble TGF-beta receptor type II (sTRII), namely KT1, KT2 and KT3, and one with an empty vector used as control vector (KV), and then investigated the effects of sTRII on the tumorigenicity of KDH-8 cells and immune responses in syngeneic Wistar King Aptekman/Hok (WKAH) rats. We found that sTRII expressed in sTRII transfectants could abolish growth inhibition of Mv1Lu cells by TGF-beta1 produced by the cells themselves, and that tumor growth of KT2 and KT3 clones in vivo was suppressed significantly compared with that of parent, KV and KT1 clones. Furthermore, we demonstrated that IL-2 production of splenocytes and IL12p40 mRNA expression in tumor tissues were restored in rats inoculated with KT2 and KT3 clones, whereas such restoration was not observed in rats inoculated with parent, KV and KT1 clones. Combined with a low expression of sTRII in KT1 tumor tissues, these results suggest that sTRII may to some extent be able to abolish the tumor-promoting activity of TGF-beta, and imply that sTRII might have a therapeutic effect on TGF-beta-producing tumors.
Division of Cancer Pathobiology, Research Section of Pathophysiology, Institute for Genetic Medicine, Hokkaido University, Kita 15, Nishi 7, Kita-Ku, Sapporo, Hokkaido 060-0815, Japan.
Wenli
W
Zhao
Masonobu
M
Kobayashi
Wei
W
Ding
Lan
L
Yuan
Prem
P
Seth
Santoso
S
Cornain
Jingxin
J
Wang
Futoshi
F
Okada
Masuo
M
Hosokawa
D000818:Animals; D017209:Apoptosis; D002453:Cell Cycle; D002460:Cell Line / Q000187:drug effects; D002999:Clone Cells / Q000473:pathology / Q000637:transplantation; D005260:Female; D007376:Interleukin-2 / Q000096:biosynthesis; D008114:Liver Neoplasms, Experimental / Q000473:pathology* / Q000628:therapy; D008168:Lung; D046911:Macromolecular Substances; D008907:Mink; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D009368:Neoplasm Transplantation; D017346:Protein Serine-Threonine Kinases; D051381:Rats; D017208:Rats, Wistar; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D012995:Solubility; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000502:physiology; D014407:Tumor Cells, Cultured / Q000473:pathology / Q000637:transplantation; D019139:Tumor Escape / Q000187:drug effects / Q000276:immunology
D007376:Interleukin-2; D046911:Macromolecular Substances; D009363:Neoplasm Proteins; D018125:Receptors, Transforming Growth Factor beta; D011993:Recombinant Fusion Proteins; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II