SCNH2 is a novel apelinergic family member acting as a potent mitogenic and chemotactic factor for both endothelial and epithelial cells

Changge Fang, Ingalill Avis, Caterina Bianco, Natalie Held, Jennifer Morris, Kris Ylaya, Stephen M. Hewitt, Alfred C. Aplin, Roberto F. Nicosia, Laura A. Fung, John D. Lewis, William G. Stetler-Stevenson, David S. Salomon, Frank Cuttitta

Angiogenesis Core Facility, Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, USA.
Department of Pathology, University of Washington, Seattle, USA.
Department of Pathology, University of Washington, Seattle, USA;Pathology and Laboratory Medicine Services, Veterans Administration Puget Sound Health Care System, Seattle, USA.
Extracellular Matrix Pathology Section, Radiation Oncology Branch, Center for Cancer Research, Bethesda, USA.
Innovascreen Inc., New Glasgow, Canada.
Innovascreen Inc., New Glasgow, Canada;Department of Oncology, University of Alberta, Edmonton, Canada.
Tissue Array Research, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, USA.
Tissue Array Research, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, USA 4Department of Pathology, University of Washington, Seattle, USA.
Tumor Growth Factor Section, Laboratory of Cancer Prevention, Center for Cancer Research, National Cancer Institute, Frederick, USA.

DOI: 10.4236/ojcd.2013.32009                

Abstract

The gut hormone apelin is a major therapeutic focus for several diseases involving inflammation and aberrant cell growth. We investigated whether apelin-36 contained alternative bioactive peptides associated with normal physiology or disease. Amino acid sequence analysis of apelin-36 identified an amidation motif consistent with the formation of a secondary bioactive peptide (SCNH2). SCNH2 is proven to be mitogenic and chemotactic in normal/malignant cells and augments angiogenesis via a PTX-resistant/CT-X-sensitive G protein-coupled receptor (GPCR). Notably, SCNH2 is substantially more potent and sensitive than apelin-13 and vascular endothelial growth factor-A. Endogenous SCNH2 is highly expressed in human tumors and placenta and in mouse embryonic tissues. Our findings demonstrate that SCNH2 is a new apelinergic member with critical pluripotent roles in angiogenesis related diseases and embryogenesis via a non-APJ GPCR.

Keywords

Novel Apelinergic Member; SCNH2; Angiogenesis; Migration; Embryogenesis

Conflicts of Interest

The authors declare no conflicts of interest.

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