title: Atrial natriuretic peptide prevents cancer metastasis through vascular endothelial cells.
abstract: Most patients suffering from cancer die of metastatic disease. Surgical removal of solid tumors is performed as an initial attempt to cure patients; however, surgery is often accompanied with trauma, which can promote early recurrence by provoking detachment of tumor cells into the blood stream or inducing systemic inflammation or both. We have previously reported that administration of atrial natriuretic peptide (ANP) during the perioperative period reduces inflammatory response and has a prophylactic effect on postoperative cardiopulmonary complications in lung cancer surgery. Here we demonstrate that cancer recurrence after curative surgery was significantly lower in ANP-treated patients than in control patients (surgery alone). ANP is known to bind specifically to NPR1 [also called guanylyl cyclase-A (GC-A) receptor]. In mouse models, we found that metastasis of GC-A-nonexpressing tumor cells (i.e., B16 mouse melanoma 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. We examined the effect of ANP on tumor metastasis in mice treated with lipopolysaccharide, which mimics systemic inflammation induced by surgical stress. 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.
authors.affiliation: Department of Biochemistry, Department of General Thoracic Surgery and.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nojiri
authors.affiliation: Department of Regenerative Medicine and Tissue Engineering.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hosoda
authors.affiliation: Department of Biochemistry.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tokudome
authors.affiliation: Department of Regenerative Medicine and Tissue Engineering.
authors.forename: Koichi
authors.initials: K
authors.lastname: Miura
authors.affiliation: Department of Biochemistry.
authors.forename: Shin
authors.initials: S
authors.lastname: Ishikane
authors.affiliation: Department of Regenerative Medicine and Tissue Engineering.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Otani
authors.affiliation: Department of Endocrinology and Metabolism, National Cerebral and Cardiovascular Center Hospital, Suita-city, Osaka 565-8565, Japan;
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kishimoto
authors.affiliation: Department of General Thoracic Surgery and.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Shintani
authors.affiliation: Department of General Thoracic Surgery and.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Inoue
authors.affiliation: Department of Biochemistry, Department of General Thoracic Surgery and.
authors.forename: Toru
authors.initials: T
authors.lastname: Kimura
authors.affiliation: Department of General Thoracic Surgery and.
authors.forename: Noriyoshi
authors.initials: N
authors.lastname: Sawabata
authors.affiliation: Department of General Thoracic Surgery and.
authors.forename: Masato
authors.initials: M
authors.lastname: Minami
authors.affiliation: Department of General Thoracic Surgery and.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Nakagiri
authors.affiliation: Department of General Thoracic Surgery and.
authors.forename: Soichiro
authors.initials: S
authors.lastname: Funaki
authors.affiliation: Department of General Thoracic Surgery, National Hospital Organization Toneyama Hospital, Toyonaka-city, Osaka, 560-8552, Japan;
authors.forename: Yukiyasu
authors.initials: Y
authors.lastname: Takeuchi
authors.affiliation: Department of General Thoracic Surgery, National Hospital Organization Toneyama Hospital, Toyonaka-city, Osaka, 560-8552, Japan;
authors.forename: Hajime
authors.initials: H
authors.lastname: Maeda
authors.affiliation: Department of Signal Transduction, Research Institute for Microbial Diseases, Suita-city, Osaka 565-0871, Japan;
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Kidoya
authors.affiliation: Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Developmental Biology, Kobe-city, Hyogo 650-0047, Japan; and.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiyonari
authors.affiliation: Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Developmental Biology, Kobe-city, Hyogo 650-0047, Japan; and.
authors.forename: Go
authors.initials: G
authors.lastname: Shioi
authors.affiliation: Department of Molecular Biology, and.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Arai
authors.affiliation: Drug Research Section II, Fukushima Research Laboratories, TOA EIYO Ltd., Fukushima-city, Fukushima 960-0280, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hasegawa
authors.affiliation: Department of Signal Transduction, Research Institute for Microbial Diseases, Suita-city, Osaka 565-0871, Japan;
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Takakura
authors.affiliation: Department of Mathematical Health Science, Osaka University Graduate School of Medicine, Suita-city, Osaka, 565-0871, Japan;
authors.forename: Megumi
authors.initials: M
authors.lastname: Hori
authors.affiliation: Department of Mathematical Health Science, Osaka University Graduate School of Medicine, Suita-city, Osaka, 565-0871, Japan;
authors.forename: Yuko
authors.initials: Y
authors.lastname: Ohno
authors.affiliation: Department of Biochemistry.
authors.forename: Mikiya
authors.initials: M
authors.lastname: Miyazato
authors.affiliation: JST-CREST/Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, Suita-city, Osaka 565-8565, Japan;
authors.forename: Naoki
authors.initials: N
authors.lastname: Mochizuki
authors.affiliation: Department of General Thoracic Surgery and.
authors.forename: Meinoshin
authors.initials: M
authors.lastname: Okumura
authors.affiliation: Department of Biochemistry, kangawa@ri.ncvc.go.jp.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kangawa
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D018572:Disease-Free Survival; D042783:Endothelial Cells / Q000166:cytology*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000473:pathology / Q000628:therapy; D008546:Melanoma, Experimental; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D012189:Retrospective Studies
chemical_list: D049452:Green Fluorescent Proteins; D009320:Atrial Natriuretic Factor
keywords: cancer metastasis; cardiac peptide; inflammation; surgery; vascular endothelial cell