A combinatorial extracellular matrix platform identifies cell-extracellular matrix interactions that correlate with metastasis
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Author(s)
Reticker-Flynn, Nathan E.
Malta, David F. Braga
Underhill, Gregory H.
Xu, Mary Jue
Winslow, Monte Meier
Hynes, Richard O
Jacks, Tyler E
Bhatia, Sangeeta N
Lamar, John
Date Issued
October 2012
Journal
Nature Communications
Publisher
Nature Publishing Group
Citation
Reticker-Flynn, Nathan E., David F. Braga Malta, Monte M. Winslow, John M. Lamar, Mary J. Xu, Gregory H. Underhill, Richard O. Hynes, Tyler E. Jacks, and Sangeeta N. Bhatia. “A Combinatorial Extracellular Matrix Platform Identifies Cell-Extracellular Matrix Interactions That Correlate with Metastasis.” Nature Communications 3 (October 9, 2012): 1122.
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Author's final manuscript
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.
MIT Department
Whitaker College of Health Sciences and Technology
Harvard University--MIT Division of Health Sciences and Technology
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
Ludwig Center for Molecular Oncology (Massachusetts Institute of Technology)
Koch Institute for Integrative Cancer Research at MIT
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1038/ncomms2128
