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

Takehito Kawakami; Tetsuro Sameshima; Hironobu Hojo; Kaori Koga; Yoshiaki Nakahara; Bryan P. Toole; Junji Suzumiya; Yasunori Okada; Akinori Iwasaki; Kazuki Nabeshima

doi:10.1186/1471-2407-11-300

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

Takehito Kawakami, Tetsuro Sameshima, Hironobu Hojo, Kaori Koga, Yoshiaki Nakahara, Bryan P. Toole, Junji Suzumiya, Yasunori Okada, Akinori Iwasaki, Kazuki Nabeshima

Department of Pathology

Research output: Contribution to journal › Article › peer-review

9 Citations (Scopus)

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.

Original language	English
Article number	300
Journal	BMC cancer
Volume	11
DOIs	https://doi.org/10.1186/1471-2407-11-300
Publication status	Published - 2011 Jul 17

ASJC Scopus subject areas

Genetics
Oncology
Cancer Research

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Synthetic emmprin peptides with chitobiose substitution stimulate MMP-2 production by fibroblasts. / Kawakami, Takehito; Sameshima, Tetsuro; Hojo, Hironobu; Koga, Kaori; Nakahara, Yoshiaki; Toole, Bryan P.; Suzumiya, Junji; Okada, Yasunori; Iwasaki, Akinori; Nabeshima, Kazuki.

In: BMC cancer, Vol. 11, 300, 17.07.2011.

Research output: Contribution to journal › Article › peer-review

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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.",

author = "Takehito Kawakami and Tetsuro Sameshima and Hironobu Hojo and Kaori Koga and Yoshiaki Nakahara and Toole, {Bryan P.} and Junji Suzumiya and Yasunori Okada and Akinori Iwasaki and Kazuki Nabeshima",

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AU - Kawakami, Takehito

AU - Sameshima, Tetsuro

AU - Hojo, Hironobu

AU - Koga, Kaori

AU - Nakahara, Yoshiaki

AU - Toole, Bryan P.

AU - Suzumiya, Junji

AU - Okada, Yasunori

AU - Iwasaki, Akinori

AU - Nabeshima, Kazuki

PY - 2011/7/17

Y1 - 2011/7/17

N2 - 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.

AB - 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.

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