Expression of Gelatinase-A (MMP-2) in Human Colon Cancer and Normal Colon Mucosa

Abstract

Proteolytic enzymes, such as type IV collagenases (MMP-2 gelatinase A, 72-kD type IV collagenase and MMP-9 gelatinase B, 92-kD type IV collagenase) play an important role in tumor invasion and metastasis. In the present study the levels of MMP-2 antigenic concentration and immunohistochemical staining were compared in paired colorectal tumor (n = 64) and background colon tissue of the same patients with clinical and pathological staging. The antigenic concentrations were found to be statistically significantly higher in cancer tissue (mean 11.29 ng/mg protein) than in corresponding normal mucosa (10.23 ng/mg protein) (p = 0.008). There was also a positive correlation between MMP-2 antigenic concentration and clinicopathologic parameters such as grade (p < 0.001) and Dukes’ stage (p = 0.001), but not with lymph node involvement. Immunohistological localization of MMP-2 was observed in tumor as well as in stromal cells. Staining intensity increased from adenoma to adenocarcinoma. The degree of staining was associated with grade (p < 0.001), Dukes’ stage (p < 0.001) and lymph node involvement (p < 0.001).

Small Integrin Binding Ligand N -Linked Glycoprotein Gene Family Expression in Different Cancers

“…The observed increase in MMP-2 expression observed in tumor samples is consistent with previous studies of breast (41,42), colon (43)(44)(45)(46)(47), stomach (48,49), lung (50 -53), rectal (43,54), and kidney cancer (55)(56)(57). Whereas a strong association of increased MMP-3 has been found in breast cancer (41, 58 -61), the increased expression levels observed in other tumor types are not as well supported by published literature.…”

The collagenase-1 (MMP-1) gene promoter polymorphism - 1607/2G is associated with favourable prognosis in patients with colorectal cancer

“…Despite this literature linking enhanced MMP production with poorer outcome for patients with cancer, the majority of these studies have been at best semi-quantitative and are a measure of expression at a single time point over the course of malignant progression (Chenard et al, 1996;Murray et al, 1996Murray et al, , 1998Adachi et al, 2001;Papadopoulou et al, 2001;Yorioka et al, 2002;Talvensaari-Mattila et al, 2003;Roeb et al, 2004;Ruokolainen et al, 2004). The discovery of polymorphisms in MMP promoters that alter gene expression has revealed strong associations between these genetic variants and increased susceptibility to the development of malignancies and other diseases (Henney et al, 2000;Ye, 2000).…”

“…They are broadly divided into the collagenases, gelatinases, stromelysins, and membrane-associatedMMPs on the basis of their substrate specificity. Overexpression of MMP-1 (Murray et al, 1996), MMP-2 (Papadopoulou et al, 2001), and MMP-3 (Roeb et al, 2004) has been linked to poor prognosis, high tumour stage, and enhanced tumour invasiveness in patients with CRC. These subjective and semiquantitative studies have inspired subsequent investigators to assess genetic polymorphisms in the promoter regions of MMP genes, as this type of DNA sequence alteration can affect cancer susceptibility and malignant phenotype (Yasui et al, 2005).…”

Platelet Aggregation-Induced by Caco-2 Cells: Regulation by Matrix Metalloproteinase-2 and Adenosine Diphosphate

“…Therefore, the precise role of this enzyme during TCIPA remains to be elucidated. MMP-2 has been previously involved in colorectal cancer in humans since this enzyme has been found in regions of tumor invasion (Papadopoulou et al, 2001;Ornstein and Cohn, 2002). In addition, a single-nucleotide polymorphism in the MMP-2 promoter region that increases gene transcriptional activity has been associated with colon cancer development and invasion (Xu et al, 2004).…”