Adrenomedullin antagonist suppresses in vivo growth of human pancreatic cancer cells in SCID mice by suppressing angiogenesis

Takahisa Ishikawa; Jian Chen; Jingxin Wang; Futoshi Okada; Toshiro Sugiyama; Takahiko Kobayashi; Masanobu Shindo; Fumihiro Higashino; Hiroyuki Katoh; Masahiro Asaka; Takeshi Kondo; Masuo Hosokawa; Masanobu Kobayashi

doi:10.1038/sj.onc.1206207

Adrenomedullin antagonist suppresses in vivo growth of human pancreatic cancer cells in SCID mice by suppressing angiogenesis

Oncogene. 2003 Feb 27;22(8):1238-42. doi: 10.1038/sj.onc.1206207.

Authors

Takahisa Ishikawa¹, Jian Chen, Jingxin Wang, Futoshi Okada, Toshiro Sugiyama, Takahiko Kobayashi, Masanobu Shindo, Fumihiro Higashino, Hiroyuki Katoh, Masahiro Asaka, Takeshi Kondo, Masuo Hosokawa, Masanobu Kobayashi

Affiliation

¹ Division of Cancer Pathology, Institute for Genetic medicine, Hokkaido University, Sapporo, Japan.

PMID: 12606950
DOI: 10.1038/sj.onc.1206207

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adrenomedullin
Angiogenesis Inhibitors / pharmacology
Angiogenesis Inhibitors / therapeutic use*
Animals
Antineoplastic Agents / pharmacology
Antineoplastic Agents / therapeutic use*
Cell Hypoxia
Gene Expression Regulation, Neoplastic
Humans
Hypoxia-Inducible Factor 1, alpha Subunit
Mice
Mice, SCID
Neoplasm Proteins / biosynthesis
Neoplasm Proteins / genetics
Neovascularization, Pathologic / drug therapy*
Pancreatic Neoplasms / blood supply
Pancreatic Neoplasms / drug therapy*
Peptide Fragments / pharmacology
Peptide Fragments / therapeutic use*
Peptides / antagonists & inhibitors*
Peptides / pharmacology
Peptides / physiology
Peptides / therapeutic use
Transcription Factors / biosynthesis
Transcription Factors / genetics
Tumor Cells, Cultured / drug effects
Xenograft Model Antitumor Assays

Substances

Angiogenesis Inhibitors
Antineoplastic Agents
HIF1A protein, human
Hypoxia-Inducible Factor 1, alpha Subunit
Neoplasm Proteins
Peptide Fragments
Peptides
Transcription Factors
adrenomedullin (22-52)
Adrenomedullin