Anti-endostatin monoclonal antibody enhances growth of human hepatocellular carcinoma cells by inhibiting activity of endostatin secreted by the transplanted cells in nude mice.
Endostatin, a fragment of collagen XVIII, inhibits angiogenesis in tumors, and is expected to become a new anticancer drug. However, its effectiveness is still controversial, because some researchers failed to reproduce the same marked regression of tumors by the peptide. We gave anti-endostatin monoclonal antibody, designated as CH18B, to nude mice transplanted with human hepatocellular carcinoma cells (JHH-1 line) that endogenously produced endostatin from collagen XVIII secreted by the cells themselves. As a result, CH18B promoted tumor angiogenesis by inhibiting endostatin activity in the tumor and subsequently increased tumor mass by preventing cancer cells from undergoing apoptosis. But the antibody itself did not stimulate proliferation of the tumor cells. Our present experimental procedure, the use of anti-endostatin antibody, definitely solved the question whether endostatin might exert its anticancer activity.
Tsuboi
So
S
Department of Hepatology, Shigei Medical Research Hospital, 2117 Yamada, Okayama 701-0202, Japan. tsuboi@shigei.or.jp
Nouso
Kazuhiro
K
Tomono
Yasuko
Y
Nagamori
Seishi
S
Naito
Ichiro
I
Watanabe
Tsunakazu
T
Manabe
Koji
K
Ohmori
Hiroyuki
H
Nakatsukasa
Harushige
H
Miyazaki
Masahiro
M
Higashi
Toshihiro
T
Shiratori
Yasushi
Y
Namba
Masayoshi
M
Ninomiya
Yoshifumi
Y
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000473:pathology* / Q000662:veterinary; D049109:Cell Proliferation; D043169:Endostatins / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008113:Liver Neoplasms / Q000276:immunology / Q000473:pathology* / Q000662:veterinary; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009374:Neoplasms, Experimental; D009389:Neovascularization, Pathologic; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D043169:Endostatins