The Matrisome: In Silico Definition and In Vivo Characterization by Proteomics of Normal and Tumor Extracellular Matrices

By Alexandra Naba, Karl R. Clauser, S. Hoersch, Hui Liu, Steven A. Carr, R. Hynes. Molecular & Cellular Proteomics, 2011

1,127 citations recorded by the source corpus.

The extracellular matrix (ECM) is a complex meshwork of cross-linked proteins providing both biophysical and biochemical cues that are important regulators of cell proliferation, survival, differentiation, and migration. We present here a proteomic strategy developed to characterize the in vivo ECM composition of normal tissues and tumors using enrichment of protein extracts for ECM components and subsequent analysis by mass spectrometry. In parallel, we have developed a bioinformatic approach to predict the in silico “matrisome” defined as the ensemble of ECM proteins and associated factors. We report the characterization of the extracellular matrices of murine lung and colon, each comprising more than 100 ECM proteins and each presenting a characteristic signature. Moreover, using human tumor xenografts in mice, we show that both tumor cells and stromal cells contribute to the production of the tumor matrix and that tumors of differing metastatic potential differ in both the tumor- and the stroma-derived ECM components. The strategy we describe and illustrate here can be broadly applied and, to facilitate application of these methods by others, we provide resources including laboratory protocols, inventories of ECM domains and proteins, and instructions for bioinformatically deriving the human and mouse matrisome.

Subfields: Cell Biology, Immunology and Allergy, Spectroscopy

View Paper: https://www.semanticscholar.org/paper/6e6c446acf88b614deb847b43a62f04593a182e0

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Citations in the corpus

Extracellular matrix remodeling in tumor progression and immune escape: from mechanisms to treatments (2023, background): “Besides gene signature, proteomic analysis of ECM proteins in cancer also contributes to identify cancer and normal tissues [558].”
Intratumor heterogeneity: the Rosetta stone of therapy resistance (2020, background): “While some tumor cells are still in contact with stroma-derived extracellular matrix, its composition is altered compared to normal tissues (Naba et al., 2012), and many tumor cells are separated from the stroma by more than one cell layer.”
Acellular normal and fibrotic human lung matrices as a culture system for in vitro investigation. (2012, background): “We identified 94 proteins in the normal lung “matrisome” (as defined in [27]), comprising 61 core ECM proteins (glycoproteins, collagens, and proteoglycans) and 33 ECM-related proteins (Table 1).”
Overview of the matrisome--an inventory of extracellular matrix constituents and functions. (2012, methodology): “…matrisome list does not include mucins, secreted C-type lectins, galectins, semaphorins, and plexins and certain other groups of proteins that plausibly do associate with the ECM but are not commonly viewed as ECM proteins; lists of these “ECM-affiliated” proteins are given in Naba et al. (2011).”
The extracellular matrix modulates the hallmarks of cancer (2014, positive): “Interestingly, many malignantly transformed cells secrete their own ECM ligands and, in doing so, are able to escape proliferative suppression to grow and survive in hostile environments [23,24].”