title: 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.
authors.affiliation: David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Nathan E
authors.initials: NE
authors.lastname: Reticker-Flynn
authors.forename: David F Braga
authors.initials: DF
authors.lastname: Malta
authors.forename: Monte M
authors.initials: MM
authors.lastname: Winslow
authors.forename: John M
authors.initials: JM
authors.lastname: Lamar
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Xu
authors.forename: Gregory H
authors.initials: GH
authors.lastname: Underhill
authors.forename: Richard O
authors.initials: RO
authors.lastname: Hynes
authors.forename: Tyler E
authors.initials: TE
authors.lastname: Jacks
authors.forename: Sangeeta N
authors.initials: SN
authors.lastname: Bhatia
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000818:Animals; D045744:Cell Line, Tumor; D005109:Extracellular Matrix / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D037502:Galectin 3 / Q000378:metabolism; D037161:Galectins / Q000378:metabolism; D007797:Laminin / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D051379:Mice
chemical_list: D005353:Fibronectins; D037502:Galectin 3; D037161:Galectins; D007797:Laminin; C526554:galectin-8, mouse