title: SMOC1 is a tenascin-C interacting protein over-expressed in brain tumors.
abstract: Tenascin-C is an extracellular matrix protein over-expressed in a large variety of cancers. In the present study, we aimed at identifying new interactors of tenascin-C by purifying secreted proteins on a tenascin-C affinity column. Analysis of eluates by mass spectrometry revealed phosphoglycerate kinase 1, clusterin, fibronectin, SPARC-related modular calcium-binding protein 1 (SMOC1) and nidogen-2 as potential interactors of tenascin-C. The interaction between tenascin-C and SMOC1 was confirmed by co-immunoprecipitation and further analyzed by Surface Plasmon Resonance Spectroscopy, which revealed an apparent dissociation constant (K(D)) value of 2.59∗10(-9)M. Further analyses showed that this binding is reduced in the presence of EDTA. To investigate whether SMOC1 itself could be over-expressed in the context of tumorigenesis, we analyzed data of two independent RNA profiling studies and found that mRNA levels of SMOC1 are significantly increased in oligodendrogliomas compared to control brain samples. In support of these data, western blot analysis of protein extracts from 12 oligodendrogliomas, 4 astrocytomas and 13 glioblastomas revealed elevated levels compared to healthy brain extract. Interestingly, cell migration experiments revealed that SMOC1 can counteract the chemo-attractive effect of tenascin-C on U87 glioma cells. The present study thus identified SMOC1 as a new cancer-associated protein capable of interacting with tenascin-C in vitro.
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Novartis Research Foundation, Basel, Switzerland. florence.brellier@fmi.ch
authors.forename: Florence
authors.initials: F
authors.lastname: Brellier
authors.forename: Sabrina
authors.initials: S
authors.lastname: Ruggiero
authors.forename: Daniela
authors.initials: D
authors.lastname: Zwolanek
authors.forename: Enrico
authors.initials: E
authors.lastname: Martina
authors.forename: Daniel
authors.initials: D
authors.lastname: Hess
authors.forename: Marianne
authors.initials: M
authors.lastname: Brown-Luedi
authors.forename: Ursula
authors.initials: U
authors.lastname: Hartmann
authors.forename: Manuel
authors.initials: M
authors.lastname: Koch
authors.forename: Adrian
authors.initials: A
authors.lastname: Merlo
authors.forename: Maddalena
authors.initials: M
authors.lastname: Lino
authors.forename: Ruth
authors.initials: R
authors.lastname: Chiquet-Ehrismann
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D002465:Cell Movement; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D047468:Immunoprecipitation; D008875:Middle Aged; D015676:Osteonectin / Q000378:metabolism*; D011485:Protein Binding; D020349:Surface Plasmon Resonance; D019063:Tenascin / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D015676:Osteonectin; C468135:SMOC1 protein, human; D019063:Tenascin