Abstract
BackgroundColorectal 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.MethodsWe 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.ResultsWe 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.ConclusionsThe 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.
Highlights
Colorectal cancer is the third most frequently diagnosed cancer and the third cause of cancer deaths in the United States
The extracellular matrix (ECM) is a major component of the tumor microenvironment and exerts many roles during tumor progression: it supports proliferation and survival of tumor cells; it contributes to the formation of the cancer stem cell niche and sustains primary tumor growth; it participates by its nature and/or architecture in the formation of a pro-invasive environment; and, it contributes to the invasion of distant sites by participating in the formation of a microenvironment that will support tumor cell seeding and growth [8,9,10]
We demonstrate in this study that we can characterize in detail the composition of the extracellular matrix of normal tissues and tumors using small samples from human colorectal cancer patients
Summary
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. Within the last five years, over 35 studies published in peer-reviewed journal applied global proteomics techniques to the study of colorectal samples from patients (reviewed in [4,5]). These studies revealed a certain number of proteins (including extracellular matrix proteins, see Results and discussion section) up or down-regulated in cancer samples as compared with normal samples, which represent potential biomarkers. The extracellular matrix (ECM) is a complex meshwork of cross-linked proteins providing architectural support for cells. The ECM appears of great interest for discovery of ways to predict, diagnose and cure cancer
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
