Open Access Highly Accessed Research article

Extracellular matrix signatures of human primary metastatic colon cancers and their metastases to liver

Alexandra Naba12*, Karl R Clauser3, Charles A Whittaker4, Steven A Carr3, Kenneth K Tanabe5 and Richard O Hynes12*

Author Affiliations

1 David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA

2 Howard Hughes Medical Institute, Massachusetts Institute of Technology, 02139 Cambridge, MA, USA

3 Proteomics Platform, Broad Institute of MIT and Harvard, 02142 Cambridge, MA, USA

4 David H. Koch Institute for Integrative Cancer Research - Barbara K. Ostrom Bioinformatics and Computing facility at the Swanson Biotechnology Center, 02139 Cambridge, MA, USA

5 Division of Surgical Oncology, Massachusetts General Hospital Cancer Center, Boston 02114, MA, USA

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BMC Cancer 2014, 14:518  doi:10.1186/1471-2407-14-518

Published: 18 July 2014

Abstract

Background

Colorectal cancer is the third most frequently diagnosed cancer and the third cause of cancer deaths in the United States. Despite the fact that tumor cell-intrinsic mechanisms controlling colorectal carcinogenesis have been identified, novel prognostic and diagnostic tools as well as novel therapeutic strategies are still needed to monitor and target colon cancer progression. We and others have previously shown, using mouse models, that the extracellular matrix (ECM), a major component of the tumor microenvironment, is an important contributor to tumor progression. In order to identify candidate biomarkers, we sought to define ECM signatures of metastatic colorectal cancers and their metastases to the liver.

Methods

We have used enrichment of extracellular matrix (ECM) from human patient samples and proteomics to define the ECM composition of primary colon carcinomas and their metastases to liver in comparison with normal colon and liver samples.

Results

We show that robust signatures of ECM proteins characteristic of each tissue, normal and malignant, can be defined using relatively small samples from small numbers of patients. Comparisons with gene expression data from larger cohorts of patients confirm the association of subsets of the proteins identified by proteomic analysis with tumor progression and metastasis.

Conclusions

The ECM protein signatures of metastatic primary colon carcinomas and metastases to liver defined in this study, offer promise for development of diagnostic and prognostic signatures of metastatic potential of colon tumors. The ECM proteins defined here represent candidate serological or tissue biomarkers and potential targets for imaging of occult metastases and residual or recurrent tumors and conceivably for therapies. Furthermore, the methods described here can be applied to other tumor types and can be used to investigate other questions such as the role of ECM in resistance to therapy.

Keywords:
Extracellular matrix; Proteomics; Colorectal cancer; Metastasis; Tumor microenvironment; Matrisome