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Nat Commun. 2017 Jan 19;8:14105. doi: 10.1038/ncomms14105.

Fibronectin-guided migration of carcinoma collectives.

Author information

1
Université Côte d'Azur, CNRS, Inserm, Institut de Biologie Valrose (iBV), Parc Valrose, 06100 Nice, France.
2
Université Côte d'Azur, Laboratoire de Pathologie Clinique et Expérimentale, Biobank [BB-0033-00025] CHU Nice-Pasteur, 06001 Nice, France.
3
Aix Marseille Univ, CNRS, INSERM, Institut Paoli-Calmettes, CRCM, Marseille Protéomique, Marseille, France.
4
Centre Antoine Lacassagne, 06189 Nice, France.
5
Biogen Inc., Cambridge, Massachusetts 02142, USA.

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.

PMID:
28102238
PMCID:
PMC5253696
DOI:
10.1038/ncomms14105
[Indexed for MEDLINE]
Free PMC Article

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