Active MMP‐2 effectively identifies the presence of colorectal cancer

Abstract

Fully active MMP-2 is expressed at such low levels in human tissues that studies often fail to confirm its value as a cancer marker despite strong associations with malignancy. Our study utilized careful extraction, accurate activity measurements, standardization to purified controls and a new statistical metric to determine whether active MMP-2 is an effective indicator of colorectal cancer compared to pro-MMP-2 or pro-MMP-9. MMP-2 and MMP-9 activities were analyzed in matched normal and cancer samples from 269 patients by gelatin zymography, computer-assisted image analysis, serial dilutions of strong samples and standardization to controls. An index of effect size was designed for comparative evaluation of active MMP-2, pro-MMP-2 and pro-MMP-9 activities. For each gelatinase, mean activity and protein levels/mg soluble protein in normal mucosa and colorectal cancer were calculated for the first time with respect to commercial standards. Active MMP-2 activity, detected in 99% of colorectal cancers, was higher in 95% of cancers (on average 10-fold) than in normal mucosa. Levels of pro-MMP-2 and pro-MMP-9, but not active MMP-9, activities were also significantly higher in cancers versus normal. However, active MMP-2 activity provided the most effective test for the presence of cancer (p < 0.0.0001) with an effect size statistically significantly larger than for either pro-MMP-2 or pro-MMP-9. Receiver operating characteristic (ROC) curves demonstrated that a cut-off for active MMP-2 of >44 SDU activity/mg soluble protein (>180 pg/mg), which is three times mean normal levels, would permit detection of colorectal cancer with an estimated sensitivity of 84% and estimated specificity of 93%. ' 2009 UICC

Encapsulated human hepatocellular carcinoma cells by alginate gel beads as an in vitro metastasis model

“…MMP2 and MMP9 are known for their ability to degrade native type IV collagen [40] and related to metastasis while MT1-MMP is a physiologic activator of proMMP2. Active MMP2 was highly expressed in cancer samples while it was very low or not detectable in normal tissues [41,42]. The ALG bead-cultured MHCC97L and HCCLM3 cells, as well as liver cancer tissue, had constantly higher gene expression of MMP2, MMP9 and MT1-MMP compared with adhesion cells (Figs.…”

The role of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) in the development of esophageal cancer

“…The gellatinases MMP-2 and MMP-9 have been studied in this regard because of their specificity for breaking down the collagen of basement membranes [39]. It has been proved that these enzymes are involved in the development of many malignant neoplasms: gastric, colorectal, pancreatic and breast cancer [40][41][42][43]. High MMP-9 protein expression in tumor tissues of EC patients has been shown in several studies [4,18,[44][45][46][47].…”

Serum matrix metalloproteinase 2 and tissue inhibitor of matrix metalloproteinases 2 in esophageal cancer patients

“…It was shown that degradation of basement membrane and invasion of epithelium is the first step of tumor development and metastasis [10]. www.fhc.viamedica.pl It was proved that matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of matrix metalloproteinases 2 (TIMP-2) are involved in tumor invasion and metastasis in case of breast, gastric, pancreatic and colorectal cancer [11][12][13][14]. It was also suggested, that MMP-2 might play an important role in carcinogenesis of esophageal squamous cell cancer (ESCC) and could act as a biological marker of invasion and lymph node metastasis in this type of tumor.…”