title: Fibronectin-guided migration of carcinoma collectives.
abstract: Functional interplay between tumour cells and their neoplastic extracellular matrix plays a decisive role in malignant progression of carcinomas. Here we provide a comprehensive data set of the human HNSCC-associated fibroblast matrisome. Although much attention has been paid to the deposit of collagen, we identify oncofetal fibronectin (FN) as a major and obligate component of the matrix assembled by stromal fibroblasts from head and neck squamous cell carcinomas (HNSCC). FN overexpression in tumours from 435 patients corresponds to an independent unfavourable prognostic indicator. We show that migration of carcinoma collectives on fibrillar FN-rich matrices is achieved through αvβ6 and α9β1 engagement, rather than α5β1. Moreover, αvβ6-driven migration occurs independently of latent TGF-β activation and Smad-dependent signalling in tumour epithelial cells. These results provide insights into the adhesion-dependent events at the tumour-stroma interface that govern the collective mode of migration adopted by carcinoma cells to invade surrounding stroma in HNSCC.
authors.affiliation: Université Côte d'Azur, CNRS, Inserm, Institut de Biologie Valrose (iBV), Parc Valrose, 06100 Nice, France.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Gopal
authors.affiliation: Université Côte d'Azur, CNRS, Inserm, Institut de Biologie Valrose (iBV), Parc Valrose, 06100 Nice, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Veracini
authors.affiliation: Université Côte d'Azur, CNRS, Inserm, Institut de Biologie Valrose (iBV), Parc Valrose, 06100 Nice, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Grall
authors.affiliation: Université Côte d'Azur, Laboratoire de Pathologie Clinique et Expérimentale, Biobank [BB-0033-00025] CHU Nice-Pasteur, 06001 Nice, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Butori
authors.affiliation: Université Côte d'Azur, CNRS, Inserm, Institut de Biologie Valrose (iBV), Parc Valrose, 06100 Nice, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Schaub
authors.affiliation: Aix Marseille Univ, CNRS, INSERM, Institut Paoli-Calmettes, CRCM, Marseille Protéomique, Marseille, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Audebert
authors.affiliation: Aix Marseille Univ, CNRS, INSERM, Institut Paoli-Calmettes, CRCM, Marseille Protéomique, Marseille, France.
authors.forename: Luc
authors.identifier: 0000-0002-1230-4787
authors.initials: L
authors.lastname: Camoin
authors.affiliation: Aix Marseille Univ, CNRS, INSERM, Institut Paoli-Calmettes, CRCM, Marseille Protéomique, Marseille, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Baudelet
authors.affiliation: Université Côte d'Azur, CNRS, Inserm, Institut de Biologie Valrose (iBV), Parc Valrose, 06100 Nice, France.
authors.forename: Agata
authors.initials: A
authors.lastname: Radwanska
authors.affiliation: Université Côte d'Azur, CNRS, Inserm, Institut de Biologie Valrose (iBV), Parc Valrose, 06100 Nice, France.|Centre Antoine Lacassagne, 06189 Nice, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Beghelli-de la Forest Divonne
authors.affiliation: Biogen Inc., Cambridge, Massachusetts 02142, USA.
authors.forename: Shelia M
authors.initials: SM
authors.lastname: Violette
authors.affiliation: Biogen Inc., Cambridge, Massachusetts 02142, USA.
authors.forename: Paul H
authors.identifier: 0000-0002-0802-0052
authors.initials: PH
authors.lastname: Weinreb
authors.affiliation: Université Côte d'Azur, CNRS, Inserm, Institut de Biologie Valrose (iBV), Parc Valrose, 06100 Nice, France.
authors.forename: Samah
authors.initials: S
authors.lastname: Rekima
authors.affiliation: Université Côte d'Azur, Laboratoire de Pathologie Clinique et Expérimentale, Biobank [BB-0033-00025] CHU Nice-Pasteur, 06001 Nice, France.
authors.forename: Marius
authors.identifier: 0000-0002-2014-1236
authors.initials: M
authors.lastname: Ilie
authors.affiliation: Université Côte d'Azur, CNRS, Inserm, Institut de Biologie Valrose (iBV), Parc Valrose, 06100 Nice, France.|Centre Antoine Lacassagne, 06189 Nice, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Sudaka
authors.affiliation: Université Côte d'Azur, Laboratoire de Pathologie Clinique et Expérimentale, Biobank [BB-0033-00025] CHU Nice-Pasteur, 06001 Nice, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Hofman
authors.affiliation: Université Côte d'Azur, CNRS, Inserm, Institut de Biologie Valrose (iBV), Parc Valrose, 06100 Nice, France.|Centre Antoine Lacassagne, 06189 Nice, France.
authors.forename: Ellen
authors.identifier: 0000-0003-2961-0059
authors.initials: E
authors.lastname: Van Obberghen-Schilling
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects* / Q000502:physiology; D005109:Extracellular Matrix; D005260:Female; D005353:Fibronectins / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms; D006801:Humans; D016023:Integrins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D005353:Fibronectins; D016023:Integrins