Adrenomedullin antagonist suppresses in vivo growth of human pancreatic cancer cells in SCID mice by suppressing angiogenesis.
Since it is reported that adrenomedullin (AM) upregulated by hypoxia inhibits hypoxic cell death, we examined the effects of AM antagonist (AM C-terminal fragment; AM(22-52)) on the growth of pancreatic cancer cells. We, for the first time, demonstrated that AM antagonist significantly reduced the in vivo growth of the pancreatic cancer cell line. Immunohistochemical analysis demonstrated that the mean diameter of blood vessels was significantly smaller in the tumor tissues treated with AM antagonist than in those treated with AM N-terminal fragment (AM(1-25)), and that the PCNA-labeling index was lower in the former than in the latter. Then we demonstrated that AM antagonist showed no effect on the in vitro growth of the pancreatic cancer cell line. These results showed that AM played an important role in the growth of pancreatic cancer cells in vivo, suggesting that AM antagonist might be a useful tool for treating pancreatic cancers.
Ishikawa
Takahisa
T
Division of Cancer Pathology, Institute for Genetic medicine, Hokkaido University, Sapporo, Japan.
Chen
Jian
J
Wang
Jingxin
J
Okada
Futoshi
F
Sugiyama
Toshiro
T
Kobayashi
Takahiko
T
Shindo
Masanobu
M
Higashino
Fumihiro
F
Katoh
Hiroyuki
H
Asaka
Masahiro
M
Kondo
Takeshi
T
Hosokawa
Masuo
M
Kobayashi
Masanobu
M
D053607:Adrenomedullin; D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015687:Cell Hypoxia; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D051379:Mice; D016513:Mice, SCID; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D010190:Pancreatic Neoplasms / Q000098:blood supply / Q000188:drug therapy*; D010446:Peptide Fragments / Q000494:pharmacology / Q000627:therapeutic use*; D010455:Peptides / Q000037:antagonists & inhibitors* / Q000494:pharmacology / Q000502:physiology / Q000627:therapeutic use; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D014407:Tumor Cells, Cultured / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D010455:Peptides; D014157:Transcription Factors; C104782:adrenomedullin (22-52); D053607:Adrenomedullin