How Heart Hormones Prevent and Suppress Metastasis of Cancers Clarified
First nationwide, multicenter clinical trials on lung cancer conducted under combined insured and uninsured system
A group of researchers from the National Cerebral and Cardiovascular Center Research institute and Osaka University clarified that protecting blood vessels by Atrial Natriuretic Peptide (ANP) prevented and suppressed metastasis of cancers.
National Cerebral and Cardiovascular Center Research institute -- NOJIRI Takashi (Head, Peptide Drug Development Laboratory, Department of Biochemistry), HOSODA Hiroshi (Head, Department of Regenerative Medicine and Tissue Engineering), TOKUDOME Takeshi (Head, Department of Information Communication), KANGAWA Kenji (Director, Research Institute)
OKUMURA Meinoshin ( Professor, General Thoratic Surgery, Graduate School of Medicine, Osaka University)
Based on this group's achievement, multicenter clinical trials on lung cancer surgeries (500 cases) will be conducted on a nationwide scale for the first time under the system for healthcare services provided combining insurance-covered and non-covered services concerning National Strategic Special Zones (Advanced Medical Care B). Participating institutes include Osaka University, The University of Tokyo, Hokkaido University, Yamagata University, Kobe University, Toneyama National Hospital, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka Prefectural Medical Center for Respiratory and Allergic Diseases, and Yamagata Prefectural Central Hospital.
ANP is a heart hormone discovered by Director Kangawa and MATSUO Hisayuki (Director Emeritus Research institute) in 1984 and has been in widespread clinical use as a medicine for treating cardiac failure.
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-non-expressing 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.
To learn more about this research, please view the full research report entitled " Atrial natriuretic peptide prevents cancer metastasis through vascular endothelial cells " at this page of the Proceedings of National Academy of Sciences of the United States of America website.
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