title: Relevance of IGFBP2 proteolysis in glioma and contribution of the extracellular protease ADAMTS1.
abstract: Expression of IGFBP2 (Insulin-like Growth Factor Binding Protein 2) has been positively correlated with glioma progression. Although the proteolysis of IGFBP2 has been widely recognized, with consequences as a major modulator of IGFII signaling, the relevance of this post-translational modification has not been well studied in tumors. Using an in vivo proteomic approach by Isotope-Coded Protein Label (ICPL), we identified IGFBP2 as a target of the extracellular protease ADAMTS1 (A Disintegrin And Metalloproteinase with ThromboSpondin motifs 1). Notably, the proteolytic pattern of IGFBP2 was also detected in human glioma culture cells and, more importantly, in all glioma samples evaluated. In addition, high expression of ADAMTS1 correlates with higher levels of cleaved IGFBP2 in glioblastoma multiforme cases. Using gene expression public databases, we confirmed that IGFBP2 is a poor prognosis marker for gliomas, and we also observed an important contribution of ADAMTS1.Finally, we showed the impact of ADAMTS1 on IGFII-mediated IGF1R phosphorylation and cellular migration. Our results support a functional interaction between IGFBP2 and ADAMTS1 and suggest the need to evaluate post-translational modifications of IGFBP2 in glioma, in order to approach new therapies.
authors: GENYO. Centre for Genomics and Oncological Research: Pfizer/Universidad de Granada/Junta de Andalucía, Granada, Spain.
authors: Estefanía
authors: E
authors: Martino-Echarri
authors: Rubén
authors: R
authors: Fernández-Rodríguez
authors: Joan Josep
authors: JJ
authors: Bech-Serra
authors: María del Carmen
authors: Mdel C
authors: Plaza-Calonge
authors: Noemi
authors: N
authors: Vidal
authors: Carmen
authors: C
authors: Casal
authors: Nuria
authors: N
authors: Colomé
authors: Joan
authors: J
authors: Seoane
authors: Francesc
authors: F
authors: Canals
authors: GENYO. Centre for Genomics and Oncological Research: Pfizer/Universidad de Granada/Junta de Andalucía, Granada, Spain.
authors: Juan Carlos
authors: JC
authors: Rodríguez-Manzaneque
mesh_terms: D051722:ADAM Proteins / Q000235:genetics* / Q000378:metabolism*; D000071097:ADAMTS1 Protein; D001932:Brain Neoplasms / Q000235:genetics*; D045744:Cell Line, Tumor; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics*; D057809:HEK293 Cells; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000235:genetics* / Q000378:metabolism*; D010766:Phosphorylation; D059748:Proteolysis; D015398:Signal Transduction; D014162:Transfection
chemical_list: D018971:Insulin-Like Growth Factor Binding Protein 2; D051722:ADAM Proteins; D000071097:ADAMTS1 Protein; C103859:ADAMTS1 protein, human