Adrenomedullin antagonist suppresses tumor formation in renal cell carcinoma through inhibitory effects on tumor endothelial cells and endothelial progenitor mobilization.

• Tsuchiya, Kunihiko

• Hida, Kyoko

• Hida, Yasuhiro

• Muraki, Chikara

• Ohga, Noritaka

• Akino, Tomoshige

• Kondo, Takeshi

• Miseki, Tetsuya

• Nakagawa, Koji

• Shindoh, Masanobu

• Harabayashi, Toru

• Shinohara, Nobuo

• Nonomura, Katsuya

• Kobayashi, Masanobu

抄録

Adrenomedullin (AM) is a multifunctional 52-amino acid peptide. AM has several effects and acts as a growth factor in several types of cancer cells. Our previous study revealed that an AM antagonist (AMA) suppressed the growth of pancreatic tumors in mice, although its mechanism was not elucidated. In this study, we constructed an AMA expression vector and used it to treat renal cell carcinoma (RCC) in mice. This AMA expression vector significantly reduced tumor growth in mice. In addition, microvessel density was decreased in AMA-treated tumors. To analyze the effect of AMA on tumor angiogenesis in this model, tumor endothelial cells (TECs) were isolated from RCC xenografts. TEC proliferation was stimulated by AM and it was inhibited by AMA significantly. AM induced migration of TECs and it was also blocked by AMA. However, normal ECs (NECs) were not affected by either AM or AMA. These results demonstrate that AMA has inhibitory effects on TECs specifically, not on NEC, thereby inhibiting tumor angiogenesis. Furthermore, we showed that vascular endothelial growth factor-induced mobilization of endothelial progenitor cell (EPC) into circulation was inhibited by AMA. These results suggest that AMA can be considered a good anti-angiogenic reagent that selectively targets TECs and EPC in renal cancer.

収録刊行物

• International journal of oncology

  International journal of oncology 36 (6), 1379-1386, 2010-06

キーワード

• Adrenomedullin/antagonists & inhibitors
• Animals
• Antineoplastic Agents/therapeutic use
• Carcinoma, Renal Cell/blood supply
• Carcinoma, Renal Cell/therapy
• Cell Line, Tumor
• Cell Proliferation
• DNA/therapeutic use
• Endothelial Cells/metabolism
• Endothelial Cells/pathology
• Female
• Gene Therapy/methods
• Humans
• Immunohistochemistry
• Kidney Neoplasms/blood supply
• Kidney Neoplasms/therapy
• Mice
• Mice, Nude
• Neovascularization, Pathologic/therapy
• Reverse Transcriptase Polymerase Chain Reaction
• Stem Cells/cytology
• Stem Cells/metabolism
• Xenograft Model Antitumor Assays

詳細情報

• CRID: 1050564288962851712
• NII論文ID: 120003370695
• HANDLE: 2115/47207
• ISSN: 17912423
• 本文言語コード: en
• 資料種別: journal article
• データソース種別:
  • IRDB
  • CiNii Articles