Angiotensin II type 1A receptor signaling facilitates tumor metastasis formation through P-selectin-mediated interaction of tumor cells with platelets and endothelial cells.

• Project/Area Number: 23592073
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Thoracic surgery
• Research Institution: Kitasato University
• Principal Investigator: AMANO Hideki 北里大学, 医学部, 講師 (60296481)
• Co-Investigator(Kenkyū-buntansha): ESHIMA Koji 北里大学, 医学部, 准教授 (30327324)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: Angiotensin II / AT1a receptor / platelets / AT1a / 血小板 / 腫瘍肺転移形成 / Angiogenesi / Patelets / アンギオテンシン / AT1a受容体 / 腫瘍肺転移

Research Abstract

Angiotensin II is involved in tumor growth, however, the precise mechanism is not known. B16F1 melanoma cells were intravenously injected into Agtr1a knockout mice (AT1a(-/-)) and wild-type littermates (WT); the AT1a(-/-) mice exhibited a reduction in lung colonies. Angiotensin II induced expression of P-selectin on platelets in WT but not in AT1a(-/-) mice. A selective P-selectin neutralizing antibody decreased lung colony numbers in WT but not in AT1a(-/-) mice. Levels of vascular endothelial growth factor (VEGF) and stromal cell-derived factor 1 (SDF-1) receptor in platelets at metastatic locus were lower in AT1a(-/-) mice. Treatment of neutralizing antibodies against VEGF and CXCR4 decreased lung colony numbers in WT but not in AT1a(-/-) mice. In AT1a(-/-) mice. These results suggest that AT1A signaling plays a critical role in tumor metastasis through P-selectin-mediated interactions of platelets with tumor and endothelial cells.

Research Products

• [Journal Article] Significant Involvement of NF-κB- inducing Kinase in Proper Differentiation ofαβandγδT cells (2014)
  • Author(s): Eshima K
  • Journal Title: Immunology Volume: 41(2) Issue: 2 Pages: 222-32
  • DOI: 10.1111/imm.12186
  • Peer Reviewed / Open Access
• [Journal Article] Aspirin reduces lung cancer metastasis to regional lymph nodes. (2014)
  • Author(s): Ogawa F., Amano H., Ito H., Matsui Y., Hosono K., Kitasato H., Satoh Y., Majima M.
  • Journal Title: Biomed Pharmacother. Volume: 68 Issue: 1 Pages: 79-86
  • DOI: 10.1016/j.biopha.2013.11.006
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• [Journal Article] Roles of microsomal prostaglandin E synthase-1 in lung metastasis formation in prostate cancer RM9 cells. (2014)
  • Author(s): Takahashi R., Amano H., Satoh T., Tabata K., Ikeda M., Kitasato H., Akira S., Iwamura M., Majima M.
  • Journal Title: Biomed Pharmacother. Volume: 68 Issue: 1 Pages: 71-77
  • DOI: 10.1016/j.biopha.2013.10.008
  • Peer Reviewed
• [Journal Article] Vascular endothelial growth factor receptor 1 signaling facilitates gastric ulcer healing and angiogenesis through the up regulation of epidermal growth factor expression on VEGFR1+ CXCR4+ cells recruited from bone marrow. (2013)
  • Author(s): Sato T., Amano H., Ito Y., Eshima K., Minamino T., Ae T., Katada C., Ohno T., Hosono K., Suzuki T., Shibuya M., Koizumi W., Majima M.
  • Journal Title: J Gastroenterol. Volume: 49 Issue: 3 Pages: 455-469
  • DOI: 10.1007/s00535-013-0869-z
  • Peer Reviewed
• [Journal Article] Angiotensin II type 1A receptor signaling facilitates tumor metastasis formation through P-selectin-mediated interaction of tumor cells with platelets and endothelial cells (2013)
  • Author(s): Amano H
  • Journal Title: Am J Pathol Volume: 182(2) Pages: 553-64
  • Peer Reviewed
• [Journal Article] Clinicopathological features and the impact of the new TNM classification of malignant tumours in patients with pulmonary large cell neuroendocrine carcinoma. (2013)
  • Author(s): Iyoda A, Jiang SX, Travis WD, Kurouzu N, Ogawa F, Amano H, Sato Y, Rusch VW, Saegusa M, Satoh Y.
  • Journal Title: Mol Clin Oncol Volume: １ Issue: 3 Pages: 437-443
  • DOI: 10.3892/mco.2013.80
  • Peer Reviewed
• [Journal Article] Angiotensin II type 1A receptor signaling facilitates tumor metastasis formation through P-selectin-mediated interaction of tumor cells with platelets and endothelial cells (2013)
  • Author(s): Amano H, Ito Y, Ogawa F, Eshima K, Suzuki T, Oba K, Matsui Y, Kato S, Fukui T, Nakamura M, Kitasato H, Fukamizu A, Majima M
  • Journal Title: Am J Pathol Volume: 182(2) Issue: 2 Pages: 553-64
  • DOI: 10.1016/j.ajpath.2012.10.026
  • Peer Reviewed
• [Journal Article] Thromboxane A_2 receptor signaling facilitates tumor colonization through P-selectin-mediated interaction of tumor cells with platelets and endothelial cells (2012)
  • Author(s): Matsui Y, Amano H, Ito Y, Eshima K, Suzuki T, Ogawa F, Iyoda A, Satoh Y, Kato S, Nakamura M, Kitasato H, Narumiya S, Majima M
  • Journal Title: Cancer Sci Volume: 103(4) Issue: 4 Pages: 700-7
  • DOI: 10.1111/j.1349-7006.2012.02200.x
  • Peer Reviewed
• [Journal Article] Ectopic expression of a T-box transcription factor, eomesodermin, renders CD4+ Th celss cytotoxic by activating both perforin-nad FasL-pathways (2012)
  • Author(s): Eshima, K, et al
  • Journal Title: Immunol Lett Volume: 144 Issue: 1-2 Pages: 7-15
  • DOI: 10.1016/j.imlet.2012.02.013
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• [Journal Article] Type II NKT cells stimulate diet-induced obesity by mediating adipose tissue inflammation, steatohepatitis and insulin resistance (2012)
  • Author(s): Satoh, M., Andoh, Y., Clingan, S. C., Ogura, H., Fujii, S., Nakayama, T., Taniguchi, M., Hirata, N., Ishimori, N., Tsutsui, H., Onoe, K. Iwabuchi, K
  • Journal Title: PLoS ONE Volume: 7(2) Issue: 2 Pages: 1-12
  • DOI: 10.1371/journal.pone.0030568
  • NAID: 120004043739
  • Peer Reviewed
• [Journal Article] Calcitoningene-related peptide facilitates revascularization during hindlimb ischemia in mice (2011)
  • Author(s): Mishima T, Ito Y, Hosono K, Tamura Y, Uchida Y, Hirata M, Suzsuki T, Amano H, Kato S, Kurihara Y, Kurihara H, Hayashi I, Watanabe M, Majima M
  • Journal Title: Am J Physiol Heart Circ Physiol Volume: 300(2) Issue: 2 Pages: 431-439
  • DOI: 10.1152/ajpheart.00466.2010
  • Peer Reviewed
• [Journal Article] Prediction of postoperative exacerbation of interstitial pneumonia in patients with lung cancer and interstitial lung disease (2011)
  • Author(s): Iyoda A, Jiang SX, 他
  • Journal Title: Exp Ther Med Volume: 2 Issue: 6 Pages: 1073-1076
  • DOI: 10.3892/etm.2011.342
  • Peer Reviewed
• [Journal Article] Expression profiling and identification of potential molecular targets for therapy in pulmonary large-cell neuroendocrine carcinoma (2011)
  • Author(s): Iyoda A, Travis WD, 他
  • Journal Title: Exp Ther Med Volume: 2 Issue: 6 Pages: 1041-1045
  • DOI: 10.3892/etm.2011.343
  • Peer Reviewed
• [Journal Article] Prediction of postoperative exacerbation of interstitial pneumonia in patients with lung cancer and interstitial lung disease (2011)
  • Author(s): Akira Iyoda, Shi-Xu Jiang, Hideki Amano, Fumihiro Ogawa, Yoshio Matui, Naomi Kurouzu, Hidenori Hara, Kenji Nezu, Tetsuo Mikami, Makoto Saegusa, Yukitoshi Satoh
  • Journal Title: EXPERIMENTAL AND THERAPEUTIC MEDICINE Volume: 2 Pages: 1073-1076
  • Peer Reviewed
• [Journal Article] Expression profiling and identification of potential molecular targets for therapy in pulmonary large-cell neuroendocrine carcinoma (2011)
  • Author(s): Akira Iyoda, William D. Travis, Inderpal S. Sarkaria, Shi-Xu Jiang, Hideki Amano, Yuichi Sato, Makoto Saegusa, Valerie W. Rusch, Yukitoshi Satoh
  • Journal Title: EXPERIMENTAL AND THERAPEUTIC MEDICINE Volume: 2 Pages: 1041-1045
  • Peer Reviewed
• [Presentation] Role of Dendritic Cells via COX-2 Derived PGE2-EP3 Signaling for Pre-metastatic Niche Formation in Lymph Node Metastasis on Lung Cancer （肺癌リンパ節転移でのPre-metastastatic nicheにおけるCOX-2誘導性PGE2-EP3シグナリングを介した樹状細胞の役割） (2014)
  • Author(s): 小川 史洋、天野 英樹、江島 耕二、細野 加奈子、佐藤 之俊、成宮 周、熊谷 雄二、馬嶋 正隆
  • Organizer: 第87回日本薬理学会年会
  • Place of Presentation: 仙台
• [Presentation] Microsomal prostaglandin E synthase-1 facilitates angiogenesis and lung metastasis formation in prostate cancer cells (マウス前立腺癌血行性肺転移モデルにおけるmPGES-1の転移メカニズムの解析) (2014)
  • Author(s): 高橋 亮、天野 英樹、佐藤 威史、岩村 正嗣、馬嶋 正隆
  • Organizer: 第87回日本薬理学会年会
  • Place of Presentation: 仙台
• [Presentation] The mechanism of Angiotensin II type 1A receptor signaling facilitates tumor metastasis formation (2013)
  • Author(s): Amano H., Ito Y., Ogawa F., Kumagai Y., Majima M.
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜日本
  • Year and Date: 2013-10-04
• [Presentation] Angiotensin Type 1a Signaling Facilitates Tumor Metastasis Formation Through P-Selectin-Mediated Interaction Of Tumor Cells With Platelets And Endothelial Cells (2013)
  • Author(s): Amano H., Ito Y., Ogawa F., Kumagai Y., Majima M
  • Organizer: American Thoracic S
  • Place of Presentation: フィラデルフィアアメリカ合衆国
  • Year and Date: 2013-05-19
• [Presentation] Angiotensin II type 1A receptor signaling facilitates tumor metastasis formation through P-selectin-mediated interaction of tumor cells with platelets and endothelial cells. (2013)
  • Author(s): Amano H, Ito Y, Ogawa F, Eshima K,
  • Organizer: American Thoracic Society
  • Place of Presentation: Philaderphia
• [Presentation] Pge2-Ep3 Signaling Induces Pre-Metastatic Niche Formation In Mediastinal Lymph Node By Cxcr4/Sdf-1 Axis (2013)
  • Author(s): Ogawa F., Amano H., Hosono K., Satoh Y., Kumaga Y., Majima M.
  • Organizer: 18th Congress of the Asian Pacific Society of Respirology
  • Place of Presentation: 横浜
• [Presentation] COX-2-Derived PGE2 Forms SDF-1-Expressing Premetastatic Niche Via EP3 Signaling In Mediastinal Lymph Node With Accumulation Of Immature Dendritic Cells (2013)
  • Author(s): Ogawa F., Amano H., Iyoda A., Satoh Y., Kumaga Y., Majima M.
  • Organizer: American Thoracic Society
  • Place of Presentation: Philaderphia
• [Presentation] Prostanoids regulate tumor stromal profiles via specific G-protein coupled receptors (2013)
  • Author(s): Majima M., Hosono K., Suzuki T., Amano H., Kato H., Ogawa F., Park K.
  • Organizer: 4th International conference on tumor-host interaction and Angiogenesis
  • Place of Presentation: Ascona, Switzerland
• [Presentation] The mechanism of Angiotensin II type 1A receptor signaling facilitates tumor metastasis formation (2013)
  • Author(s): Amano H., Ito Y., Ogawa F., Kumagai Y., Majima M.
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] Thromboxane A2 receptor signaling facilitates tumor colonization through P-selectin-mediated interaction of tumor cells with platelets and endothelial cells (2011)
  • Author(s): Matsui Y, Amano H, Ito Y, Eshima K, Suzuki T, Ogawa F, Iyoda A, Satoh Y, Kato S, Nakamura M, Kitasato H, Narumiya S, Majima M.
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Remarks]
  • URL: http://www.med.kitasato-u.ac.jp/pharm/index.html
• [Remarks] 北里大学医学部薬理学教室
  • URL: http://www.med.kitasato-u.ac.jp/pharm/index.html