Synthetic emmprin peptides with chitobiose substitution stimulate MMP-2 production by fibroblasts

BMC Cancer

Research Article

Hironobu Hojo¹  Yoshiaki Nakahara¹  Tetsuro Sameshima²  Kazuki Nabeshima³  Kaori Koga³  Takehito Kawakami⁴  Yasunori Okada⁵  Bryan P Toole⁶  Akinori Iwasaki⁷  Junji Suzumiya⁸ 

[1] Department of Applied Biochemistry, Institute of Glycotechnology, Tokai University, 1117 Kitakinme, Hiratsuka, 259-1292, Kanagawa, Japan;Department of Neurosurgery, NTT Medical Center Tokyo, 5-9-22 Higashigotanda, Shinagawa-ku, 141-8625, Tokyo, Japan;Department of Pathology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, 814-0180, Fukuoka, Japan;Department of Pathology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, 814-0180, Fukuoka, Japan;Department of Thoracic Surgery, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, 814-0180, Fukuoka, Japan;Department of Pathology, Keio University School of Medicine, 35 Shinanomachi, 160-0016, Tokyo, Japan;Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, 173 Ashley Avenue, 29425, Charleston, SC, USA;Department of Thoracic Surgery, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, 814-0180, Fukuoka, Japan;Shimane University Hospital Cancer Center, 89-1 Enya, Izumo, 693-8501, Shimane, Japan;

关键词: GlcNAc;    Epithelioid Sarcoma;    Nodular Fasciitis;    Chitobiose;    Lactalbumin Hydrolysate;   

DOI  :  10.1186/1471-2407-11-300

 received in 2011-02-21, accepted in 2011-07-17,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundEmmprin, a glycoprotein containing two Ig domains, is enriched on tumor cell surfaces and stimulates matrix metalloproteinase (MMP) production by adjacent stromal cells. Its first Ig domain (ECI) contains the biologically active site. The dependence of emmprin activity on N-glycosylation is controversial. We investigated whether synthetic ECI with the shortest sugar is functionally active.MethodsThe whole ECI peptides carrying sugar chains, a chitobiose unit or N-linked core pentasaccharide, were synthesized by the thioester method and added to fibroblasts to examine whether they stimulate MMP-2 production.ResultsECI carrying a chitobiose unit, ECI-(GlcNAc) 2, but not ECI without a chitobiose unit or the chitobiose unit alone, dose-dependently stimulated MMP-2 production by fibroblasts. ECI with longer chitobiose units, ECI-[(Man)3(GlcNAc)2], also stimulated MMP-2 production, but the extent of its stimulation was lower than that of ECI-(GlcNAc)2.ConclusionsOur results indicate that ECI can mimic emmprin activity when substituted with chitobiose, the disaccharide with which N-glycosylation starts.

【 授权许可】

Unknown   
© Kawakami et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.