TY - JOUR
T1 - Synthetic emmprin peptides with chitobiose substitution stimulate MMP-2 production by fibroblasts
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
N1 - Funding Information:
The authors thank Ms. M. Onitsuka for the skillful assistance in cell culture and co-culture experiments. This work was supported in part by a Grant-in-Aid for Scientific Research (No. 20590415) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, a grant from the Research Center for Advanced Molecular Medicine, Fukuoka University, and NIH grant CA082867.
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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U2 - 10.1186/1471-2407-11-300
DO - 10.1186/1471-2407-11-300
M3 - Article
C2 - 21762534
AN - SCOPUS:79960558375
VL - 11
JO - BMC Cancer
JF - BMC Cancer
SN - 1471-2407
M1 - 300
ER -
