TY - JOUR
T1 - Suppression of in vivo tumorigenicity of rat hepatoma cell line KDH-8 cells by soluble TGF-β receptor type II
AU - Zhao, Wenli
AU - Kobayashi, Masonobu
AU - Ding, Wei
AU - Yuan, Lan
AU - Seth, Prem
AU - Cornain, Santoso
AU - Wang, Jingxin
AU - Okada, Futoshi
AU - Hosokawa, Masuo
N1 - Funding Information:
Acknowledgements This study was supported in part by a grant-in-aid from the Japanese Ministry of Education, Culture, Sports, Science and Technology.
PY - 2002
Y1 - 2002
N2 - We have previously reported that transforming growth factor beta (TGF-β) 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-β production by low-dose bleomycin restored these activities significantly. In this study, we established three transfectant clones with stable expression of soluble TGF-β 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-β1 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-β, and imply that sTRII might have a therapeutic effect on TGF-β-producing tumors.
AB - We have previously reported that transforming growth factor beta (TGF-β) 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-β production by low-dose bleomycin restored these activities significantly. In this study, we established three transfectant clones with stable expression of soluble TGF-β 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-β1 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-β, and imply that sTRII might have a therapeutic effect on TGF-β-producing tumors.
KW - Immunorestoration
KW - Rat hepatocarcinoma
KW - TGF-β
KW - TGF-β receptor type II
UR - http://www.scopus.com/inward/record.url?scp=0036038212&partnerID=8YFLogxK
U2 - 10.1007/s00262-002-0290-6
DO - 10.1007/s00262-002-0290-6
M3 - Article
C2 - 12192538
AN - SCOPUS:0036038212
SN - 0340-7004
VL - 51
SP - 381
EP - 388
JO - Cancer Immunology, Immunotherapy
JF - Cancer Immunology, Immunotherapy
IS - 7
ER -
