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Open Access Research article

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

Takehito Kawakami12, Tetsuro Sameshima3, Hironobu Hojo4, Kaori Koga1, Yoshiaki Nakahara4, Bryan P Toole5, Junji Suzumiya6, Yasunori Okada7, Akinori Iwasaki2 and Kazuki Nabeshima1*

Author Affiliations

1 Department of Pathology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan

2 Department of Thoracic Surgery, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan

3 Department of Neurosurgery, NTT Medical Center Tokyo, 5-9-22 Higashigotanda, Shinagawa-ku, Tokyo 141-8625, Japan

4 Department of Applied Biochemistry, Institute of Glycotechnology, 1117 Kitakinme, Hiratsuka, Tokai University, Kanagawa 259-1292, Japan

5 Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA

6 Shimane University Hospital Cancer Center, 89-1 Enya, Izumo, Shimane 693-8501 Japan

7 Department of Pathology, Keio University School of Medicine, 35 Shinanomachi, Tokyo 160-0016, Japan

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BMC Cancer 2011, 11:300  doi:10.1186/1471-2407-11-300

Published: 17 July 2011

Abstract

Background

Emmprin, 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.

Methods

The 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.

Results

ECI 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.

Conclusions

Our results indicate that ECI can mimic emmprin activity when substituted with chitobiose, the disaccharide with which N-glycosylation starts.