A combinatorial extracellular matrix platform identifies cell-extracellular matrix interactions that correlate with metastasis
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; ... Show more Show less
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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.
DepartmentWhitaker 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
Nature Publishing Group
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.
Author's final manuscript