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A combinatorial extracellular matrix platform identifies cell-extracellular matrix interactions that correlate with metastasis.

Abstract：

:Extracellular matrix interactions have essential roles in normal physiology and many pathological processes. Although the importance of extracellular matrix interactions in metastasis is well documented, systematic approaches to identify their roles in distinct stages of tumorigenesis have not been described. Here we report a novel-screening platform capable of measuring phenotypic responses to combinations of extracellular matrix molecules. Using a genetic mouse model of lung adenocarcinoma, we measure the extracellular matrix-dependent adhesion of tumour-derived cells. Hierarchical clustering of the adhesion profiles differentiates metastatic cell lines from primary tumour lines. Furthermore, we uncovered that metastatic cells selectively associate with fibronectin when in combination with galectin-3, galectin-8 or laminin. We show that these molecules correlate with human disease and that their interactions are mediated in part by α3β1 integrin. Thus, our platform allowed us to interrogate interactions between metastatic cells and their microenvironments, and identified extracellular matrix and integrin interactions that could serve as therapeutic targets.

journal_name

Nat Commun

journal_title

Nature communications

authors

Reticker-Flynn NE,Malta DF,Winslow MM,Lamar JM,Xu MJ,Underhill GH,Hynes RO,Jacks TE,Bhatia SN

doi

10.1038/ncomms2128

subject

Has Abstract

pub_date

2012-01-01 00:00:00

pages

1122

issn

2041-1723

pii

ncomms2128

journal_volume

3

pub_type

杂志文章

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