Serum levels and tissue expression of matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of metalloproteinases 2 (TIMP-2) in colorectal cancer patients

Magdalena Groblewska,Anna Pryczynicz,Bogusław Kędra,Barbara Mroczko,Katarzyna Guzińska-Ustymowicz,Andrzej Kemona,Mariusz Gryko,Maciej Szmitkowski

doi:10.1007/s13277-013-1502-8

Abstract

The objective of the study was the assessment of serum levels and tissue expression of matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of matrix metalloproteinases 2 (TIMP-2) in patients with colorectal cancer (CRC). The study included 72 CRC patients and 68 healthy subjects. The serum levels of MMP-2 and TIMP-2 were measured using enzyme-linked immunosorbent assay (ELISA) method, whereas tissue expression of MMP-2 and TIMP-2 in cancer cells, interstitial inflammatory cells, and adjacent normal colorectal mucosa were examined by immunohistochemical staining of tumor samples. The serum levels of MMP-2 and TIMP-2 in cancer patients were significantly lower than those in control group, but the percentage of positive immunoreactivity of these proteins were higher in malignant and inflammatory cells as compared to normal tissue. There was a significant correlation between MMP-2 immunoreactivity in inflammatory cells and the presence of distant metastases and between TIMP-2 expression in inflammatory cells and tumor size, nodal involvement, and distant metastases. Area under receiver operating characteristic (ROC) curve (AUC) for serum MMP-2 was higher than for serum TIMP-2. Moreover, positive tissue expression of MMP-2 was a significant prognostic factor for CRC patients’ survival. Our findings suggest that MMP-2 and TIMP-2 might play a role in the process of colorectal cancer invasion and metastasis, but the significance of their interactions with tumor stroma and interstitial inflammatory infiltration in colorectal neoplasia require further elucidation.

Highlights

Colorectal cancer (CRC) is one of the most frequent malignant tumors in the industrialized world [1]
Our findings suggest that matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of matrix metalloproteinases 2 (TIMP-2) might play a role in the process of colorectal cancer invasion and metastasis, but the significance of their interactions with tumor stroma and interstitial inflammatory infiltration in colorectal neoplasia require further elucidation
The serum levels of MMP-2 and tissue inhibitors of matrix metalloproteinases (TIMPs)-2 were significantly lower in CRC patients than in healthy subjects and decreased with tumor stage [14]

Summary

Introduction

Colorectal cancer (CRC) is one of the most frequent malignant tumors in the industrialized world [1]. Colorectal carcinogenesis is a complex, long-term process and includes several steps of malignant transformation from normal epithelium to cancer cells, which involves numerous genetic changes and results in various phenotypic alterations [2]. The step of tumor development is the degradation of basement membrane and invasion of epithelium that leads to metastasis of cancer cells into distant organs [3]. Matrix metalloproteinase 2 (MMP-2) and MMP-9, known as gelatinases, have been implicated to play a significant role in colon cancer progression and metastasis. Levels of the MMP-2 gene expression in colorectal tumors were lower than in adjacent normal mucosa and significantly correlated with the depth of invasion, venous invasion, and presence of liver metastasis [4].

Objectives

Methods

Results