Synthetic Emmprin Peptides with Chitobiose Substitution Stimulate MMP-2 Production by Fibroblasts

Overview

Journal BMC Cancer

Publisher Biomed Central

Specialty Oncology

Date 2011 Jul 19

PMID 21762534

Citations 5

Authors

Takehito Kawakami

Tetsuro Sameshima

Hironobu Hojo

Kaori Koga

Yoshiaki Nakahara

Bryan P Toole

Junji Suzumiya

Yasunori Okada

Akinori Iwasaki

Kazuki Nabeshima

Affiliations

Soon will be listed here.

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.

Citing Articles

CD73 complexes with emmprin to regulate MMP-2 production from co-cultured sarcoma cells and fibroblasts.

Aoki M, Koga K, Miyazaki M, Hamasaki M, Koshikawa N, Oyama M BMC Cancer. 2019; 19(1):912.

PMID: 31510956 PMC: 6739984. DOI: 10.1186/s12885-019-6127-x.

How, with whom and when: an overview of CD147-mediated regulatory networks influencing matrix metalloproteinase activity.

Grass G, Toole B Biosci Rep. 2015; 36(1):e00283.

PMID: 26604323 PMC: 4718507. DOI: 10.1042/BSR20150256.

Importance of N-glycosylation on CD147 for its biological functions.

Bai Y, Huang W, Ma L, Jiang J, Chen Z Int J Mol Sci. 2014; 15(4):6356-77.

PMID: 24739808 PMC: 4013633. DOI: 10.3390/ijms15046356.

The glycosylated IgII extracellular domain of EMMPRIN is implicated in the induction of MMP-2.

Papadimitropoulou A, Mamalaki A Mol Cell Biochem. 2013; 379(1-2):107-13.

PMID: 23716178 DOI: 10.1007/s11010-013-1632-8.

Regulation of invadopodia formation and activity by CD147.

Grass G, Bratoeva M, Toole B J Cell Sci. 2012; 125(Pt 3):777-88.

PMID: 22389410 PMC: 3367836. DOI: 10.1242/jcs.097956.

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