Atrial natriuretic peptide prevents cancer metastasis through vascular endothelial cells.

• Project/Area Number: 26461393
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Endocrinology
• Research Institution: National Cardiovascular Center Research Institute
• Principal Investigator: HOSODA HIROSHI 国立研究開発法人国立循環器病研究センター, 研究所, 室長 (40359807)
• Co-Investigator(Renkei-kenkyūsha): KANGAWA KENJI 国立循環器病研究センター研究所, 研究所長 (00112417)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 血管内分泌学

Outline of Final Research Achievements

The aim of this study was to investigate the mechanism of atrial natriuretic peptide (ANP) in the prevention of cancer metastasis.
We have previously reported that ANP treatment during the perioperative period reduces inflammatory response and has a prophylactic effect on postoperative cardiopulmonary complications in lung cancer surgery.
ANP is known to bind specifically to guanylyl cyclase-A (GC-A) receptor. In mouse models, metastasis of GC-A-nonexpressing tumor cells to the lung was increased in vascular endothelium-specific GC-A knockout mice and decreased in vascular endothelium-specific GC-A transgenic mice compared with control mice. ANP inhibited the adhesion of cancer cells to pulmonary arterial and micro-vascular endothelial cells by suppressing the E-selectin expression that is promoted by inflammation. These results suggest that ANP prevents cancer metastasis by inhibiting the adhesion of tumor cells to inflamed endothelial cells.

Research Products

• [Journal Article] Atrial natriuretic peptide protects against bleomycin-induced pulmonary fibrosis via vascular endothelial cells in mice : ANP for pulmonary fibrosis. (2017)
  • Author(s): Okamoto A, Nojiri T, Konishi K, Tokudome T, Miura K, Hosoda H, Hino J, Miyazato M, Kyomoto Y, Asai K, Hirata K, Kangawa K
  • Journal Title: Respir Res Volume: 18 Issue: 1 Pages: 1-1
  • DOI: 10.1186/s12931-016-0492-7
  • Peer Reviewed / Open Access
• [Journal Article] Myeloprotective effects of C-type natriuretic peptide on cisplatin-induced bone marrow granulocytopenia in mice. (2017)
  • Author(s): Zenitani M, Nojiri T, Kimura T, Hosoda H, Miura K, Hino J, Nakahata K, Uehara S, Miyazato M, Oue T, Okuyama H, Kangawa K
  • Journal Title: Cancer Chemother Pharmacol Volume: 79 Issue: 2 Pages: 363-368
  • DOI: 10.1007/s00280-016-3221-5
  • Peer Reviewed / Open Access
• [Journal Article] C-type natriuretic peptide in combination with sildenafil attenuates proliferation of rhabdomyosarcoma cells. (2016)
  • Author(s): Zenitani M, Nojiri T, Uehara S, Miura K, Hosoda H, Kimura T, Nakahata K, Miyazato M, Okuyama H, Kangawa K.
  • Journal Title: Cancer Med. Volume: 5 Issue: 5 Pages: 795-805
  • DOI: 10.1002/cam4.642
  • Peer Reviewed / Open Access
• [Journal Article] Atrial natriuretic peptide protects against cisplatin-induced granulocytopenia. (2016)
  • Author(s): Nojiri T, Hosoda H, Zenitani M, Tokudome T, Kimura T, Miura K, Miyazato M, Okumura M, Kangawa K
  • Journal Title: Cancer Chemother Pharmacol Volume: 78 Issue: 1 Pages: 191-197
  • DOI: 10.1007/s00280-016-3075-x
  • Peer Reviewed / Open Access
• [Journal Article] C-type natriuretic peptide ameliorates pulmonary fibrosis by acting on lung fibroblasts in mice. (2016)
  • Author(s): Kimura T, Nojiri T, Hino J, Hosoda H, Miura K, Shintani Y, Inoue M, Zenitani M, Takabatake H, Miyazato M, Okumura M, Kangawa K.
  • Journal Title: Respiratory research Volume: 17 Issue: 1 Pages: 19-19
  • DOI: 10.1186/s12931-016-0335-6
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Exacerbation of bleomycin-induced injury by lipopolysaccharide in mice: establishment of a mouse model for acute exacerbation of interstitial lung diseases. (2015)
  • Author(s): Kimura T, Nojiri T, Hosoda H, Shintani Y, Inoue M, Miyazato M, Okumura M, Kangawa K.
  • Journal Title: European journal of cardio-thoracic surgery Volume: 48 Issue: 4 Pages: e85-e91
  • DOI: 10.1093/ejcts/ezv261
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Protective effects of C-type natriuretic peptide on cisplatin-induced nephrotoxicity in mice (2015)
  • Author(s): Kimura, T., Nojiri, T., Hosoda, H., Ishikane, S., Shintani, Y., Inoue, M., Miyazato, M., Okumura, M., Kangawa, K.
  • Journal Title: Cancer Chemotherapy and Pharmacology Volume: 75(5) Issue: 5 Pages: 1057-1063
  • DOI: 10.1007/s00280-015-2734-7
  • Peer Reviewed / Open Access
• [Journal Article] Atrial natriuretic peptide prevents cancer metastasis through vascular endothelial cells. (2015)
  • Author(s): Nojiri T, Hosoda H, Tokudome T, Miura K, Ishikane S, Otani K, Kishimoto I, Shintani Y, Inoue M, Kimura T, Sawabata N, Minami M, Nakagiri T, Funaki S, Takeuchi Y, Maeda H, Kidoya H, Kiyonari H, Shioi G, Arai Y, Hasegawa T, Takakura N, Hori M, Ohno Y, Miyazato M, Mochizuki N, Okumura M, Kangawa K
  • Journal Title: Proc Natl Acad Sci USA Volume: 112 Issue: 13 Pages: 4086-4091
  • DOI: 10.1073/pnas.1417273112
  • Peer Reviewed / Open Access
• [Presentation] ANPの血管内皮細胞の接着分子制御による癌細胞の転移抑制効果について (2015)
  • Author(s): 細田洋司、野尻崇、石兼真、三浦浩一、宮里幹也、寒川賢治
  • Organizer: 第88回日本内科学会学術総会
  • Place of Presentation: 東京
  • Year and Date: 2015-04-23 – 2015-04-25
• [Presentation] ANPの血管内皮細胞の接着分子制御による癌細胞の転移抑制効果について (2015)
  • Author(s): 細田洋司、野尻崇、石兼真、三浦浩一、宮里幹也、寒川賢治
  • Organizer: 第88回日本内分泌学会学術総会
  • Place of Presentation: 東京
  • Year and Date: 2015-04-23