Matrisome Project

Introduction

The extracellular matrix (ECM) is a fundamental and important component of metazoan organisms providing architectural support and anchorage for the cells. The ECM consists of a complex meshwork of highly cross-linked proteins and exists as interstitial forms within organs and as specialized forms, such as basement membranes underlying epithelia, vascular endothelium and surrounding certain other tissues and cell types.

In a research effort bringing together scientists from the Koch Institute for Integrative Cancer Research at MIT and the Broad Institute of MIT and Harvard, we characterized and predicted bioinformatically the ensemble of genes encoding the "matrisome", i.e. the ensemble of extracellular matrix and ECM-associated proteins (Naba et al, 2011). This effort was aided by a key feature of extracellular matrix proteins: their characteristic domain-based organization.

In collaboration with the Proteomics Platform of the Broad Institute, we developed a proteomics pipeline to characterize the composition of tissue and tumor extracellular matrices. Using this pipeline, we have demonstrated that any given tissue or tumor comprises 150+ ECM proteins. We also found that there are reproducible and characteristic differences between tissues and tumors which allow the definition of tissue- or tumor-specific ECM signatures.

We have now established a dedicated web site  http://matrisomeproject.mit.edu

to provide easy access to information and resources relevant to research on ECM proteins and to be a platform for deploying data collections, methods, and protocols. This effort is aimed at further facilitating the use of our protocols by other scientists and to allow their widespread use in future studies.

 

Publications

  1. Naba A, Clauser KR, Hoersch S, Liu H, Carr SA, Hynes RO.  (2012).  The matrisome: in silico definition and in vivo characterization by proteomics of normal and tumor extracellular matrices. (2012).  Mol. Cell. Proteomics 11(4): M111.014647.   doi:10.1074/mcp.M111.014647). PMID:22159717
  2. Hynes RO, Naba A. (2012). Overview of the Matrisome—An Inventory of Extracellular Matrix Constituents and Functions. Cold Spring Harbor Perspectives in Biology (2012)  PMID:21937732. In: Hynes RO, Yamada KM (Editors). Extracellular Matrix Biology. Cold Spring Harbor Perspectives in Biology (2012).
  3. Naba A, Hoersch S, Hynes RO. (2012). Towards definition of an ECM parts list: An advance on GO categories. Matrix Biology 31(7-8):371-372. (doi: 10.1016/j.matbio.2012.11.008). PMID:23199376.
  4. Naba A, Clauser K.R, Lamar, Carr S.A, and Hynes R.O. (2014). Extracellular matrix signatures of human mammary carcinoma identify novel metastasis promoters. eLife 3:e01308. (doi: 10.7554/eLife.01308). PMID:24618895.
  5. Naba A, Clauser K.R, Whittaker C.A, Carr S.A, Tanabe K.K and Hynes R.O. (2014).  Extracellular matrix signatures of human primary metastatic colon cancers and their metastases to liver. BMC Cancer,14(1):518. PMID:25037231 [Abstract in PubMed] [Full Text]
  6. Naba A, Clauser K.R, Hynes R.O. (2015). Enrichment of Extracellular Matrix Proteins from Tissues and Digestion into Peptides for Mass Spectrometry Analysis. J Vis Exp.2015 Jul 23; (101) PMID: 26273955
  7. Naba A, Clauser K.R, Ding H. Whittaker C.A, Carr S.A, Hynes R.O. (2015). The Extracellular Matrix: Tools and Insights for the "omics" era. Matrix Biol 2015 Jul 8. PMID:26163349

People, Institutions and Funding

The Hynes Lab at The Koch Institute for Integrative Cancer Research at MIT

Alexandra Naba
Richard Hynes

The Barbara K. Ostrom (1978) Bioinformatics & Computing Facility at the Swanson Biotechnology Center

Huiming Ding
Charlie Whittaker
Sebastian Hoersch

 

Collaborators

Proteomics Platform of The Broad Institute of MIT and Harvard
Karl R. Clauser
Steven A. Carr

 

Sponsors

Howard Hughes Medical Institute (HHMI)
Tumor Microenvironment Network

 

 

 

 

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