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BMC Cancer DOI:10.1186/1471-2407-14-518

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

Publication TypeJournal Article
Year of Publication2014
AuthorsNaba, A, Clauser, KR, Whittaker, CA, Carr, SA, Tanabe, KK, Hynes, RO
JournalBMC Cancer
Volume14
Pages518
Date Published2014 Jul 18
ISSN1471-2407
KeywordsBiomarkers, Tumor, Colonic Neoplasms, Extracellular Matrix, Extracellular Matrix Proteins, Gene Expression Regulation, Neoplastic, Humans, Liver Neoplasms, Proteomics
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.

URLhttp://www.biomedcentral.com/1471-2407/14/518
DOI10.1186/1471-2407-14-518
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/25037231?dopt=Abstract

Alternate JournalBMC Cancer
PubMed ID25037231
PubMed Central IDPMC4223627
Grant ListCA163109 / CA / NCI NIH HHS / United States
P30-CA14051 / CA / NCI NIH HHS / United States
U54 CA126515 / CA / NCI NIH HHS / United States
/ / Howard Hughes Medical Institute / United States