Adrenomedullin antagonist suppresses tumor formation in renal cell carcinoma through inhibitory effects on tumor endothelial cells and endothelial progenitor mobilization.
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概要
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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.
著者
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Takeuchi Jin
Department Of Hematology And Rheumatology Nihon University School Of Medicine
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Kondo Takeshi
Stem Cell Transplantation Center Hokkaido University Hospital
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Moriuchi Tetsuya
Hokkaido Urothelial Cancer Research Group
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Kawamura Takahito
Department Of Medicine Ii Hokkaido University Graduate School Of Medicine
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Moriuchi Tetsuya
Department Of Cell Biology Tokai University School Of Medicine
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Moriuchi Tetsuya
Division Of Cancer-related Genes Institute For Genetic Medicine Hokkaido University
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Kawaguchi Motoko
Department Of Surgical Pathology Tokyo Women's Medical University
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Kobayashi M
Department Of Public Health Social Medicine And Medical Informatics Ehime University Graduate School
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Tsuchiya Kunihiko
Department Of Urology Hokkaido University School Of Medicine
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Kondo Takeshi
北海道大学 医学研究科消化器内科学
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Kobayashi M
Departments Of Pathology Tokyo Women
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Nonomura Katsuya
Department Of Urology Hokkaido University Graduate School Of Medicine
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Shinohara Nobuo
Department Of Urology Hokkaido University Graduate School Of Medicine
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Ohga Noritaka
Department Of Vascular Biology Hokkaido University Graduate School Of Dental Medicine
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Muraki Chikara
Department Of Oral Pathology And Biology Division Of Oral Pathological Science University Of Hokkaid
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Hayashi Yasuhiro
Department Of Surgical Oncology Graduate School Of Medicine Hokkaido University
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Tsuchiya Kunihiko
Department Of Renal And Genitourinary Surgery Graduate School Of Medicine University Of Hokkaido
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Kondo Takeshi
Department Of Medicine Ii Hokkaido University Graduate School Of Medicine
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Kondo Takeshi
Department Of Gastroenterology And Hematology Hokkaido University Graduate School Of Medicine
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Harabayashi Toru
Department Of Renal And Genitourinary Surgery Graduate School Of Medicine Hokkaido University
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Tanaka Junji
Japan Society For Hematopoietic Cell Transplantation Adult Data Management Committee
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Hida Kyoko
Department Of Oral Pathology And Biology Division Of Vascular Biology Hokkaido University
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Shindoh Masanobu
Division Of Oral Pathobiological Science Graduate School Of Dental Medicine Hokkaido University
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Shindoh Masanobu
Department Of Oral Pathology And Biology Hokkaido University Graduate School Of Dental Medicine
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Shindoh Masanobu
Department Of Oral Pathology And Biology Division Of Oral Pathobiological Science Hokkaido Universit
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Kondo Takeshi
Department Of Pathology Laboratory Of Cancer Research Hokkaido University Graduate School Of Medicine
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Tanaka Shinya
Department Of Pathology Laboratory Of Cancer Research Hokkaido University Graduate School Of Medicine
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