Association of matrilysin-2 (MMP-26) expression with tumor progression and activation of MMP-9 in esophageal squamous cell carcinoma

Abstract

Expression of matrilysin-2, matrix metalloproteinase (MMP)-26, has been implicated in the progression of several types of human cancer. Matrilysin-2 has been reported to be a physiological and pathological activator of pro-MMP-9. The aim of this study was to examine matrilysin-2 expression and determine whether it is correlated with progression of human esophageal squamous cell carcinoma (ESCC). Semi-quantitative reverse transcriptase-polymerase chain reaction, immunohistochemical analysis, zymography and an in vitro invasion assay were performed. Matrilysin-2 mRNA expression was undetectable or only faintly detected in non-tumor tissues, but its overexpression was detected in 24 of the 50 ESCC tissues. Matrilysin-2 overexpression was significantly correlated with depth of invasion, lymph node metastasis and an advance in pathological tumor node metastasis (pTNM) stage. Sections with immunostaining signals in >10% of carcinoma cells at the invasive front, which were observed in 46 of 100 cases, were judged to be positive for matrilysin-2 expression. Matrilysin-2 expression was significantly correlated with depth of invasion, lymph node and distant metastasis, advance in pTNM stage and recurrence. Expression of matrilysin-2 was significantly correlated with nuclear beta-catenin expression and MMP-9 expression. Patients with matrilysin-2-positive cancer had significantly shorter overall and disease-free survival periods than did those with matrilysin-2-negative cancer. Matrilysin-2 expression retained its significant predictive value for overall and disease-free survival in multivariate analysis. Moreover, patients with concomitant expression of matrilysin-2 and MMP-9 had the worst prognosis. Zymography revealed that matrilysin-2 expression was significantly correlated with expression of active MMP-9 in ESCC tissues. Matrilysin-2-transfected TE-1 ESCC cells showed active MMP-9 activity and were more invasive in vitro compared with mock-transfected TE-1 cells. The results of this study suggest that matrilysin-2, the expression of which is closely correlated with nuclear beta-catenin expression and active MMP-9 activity, plays a key role in the progression of ESCC.

Increased expression of matrix metalloproteinases-21 and -26 and TIMP-4 in pancreatic adenocarcinoma

“…24,46 However, in esophageal SCC, MMP-26 overexpression correlates strongly with depth of invasion, lymph node and distant metastases. 47 In our material, MMP-26 was expressed by cancer cells in 52% of the adenocarcinomas examined. As seen with MMP-21, positivity was found in moderately differentiated but not in poorly differentiated cells.…”

Immunohistochemical expression of MMPs 1, 7, and 26 in syndrome and nonsyndrome odontogenic keratocysts

“…Therefore, deregulation of the WNT signaling pathway is implicated in the overexpression of matrilysins in many epithelial neoplasms, such as colorectal and esophageal carcinomas, contributing to local invasiveness and metastasis. 24,25,29 Despite the conspicuous expression of MMPs-7 and Ϫ26 in epithelial neoplasms, 28,29 our results showed a mild immunoreactivity to these proteases in the cytoplasm of few mesenchymal cells in SOKC and NSOKC connective tissues. Unfortunately, this scant immunoreactivity was not sufficient to be considered as a positive pattern, according to the parameters used in our research.…”

“…14,[24][25][26] Matrilysins differ from other MMPs in their low molecular weight, by their lack of a C-terminal hemopexin domain common to other MMPs, 26,27 and their conspicuous expression in epithelial cells. 28,29 Despite reports describing the importance of matrilysins in normal glandular epithelium 22,25,29 as well as in malignant epithelial neoplasms, 24,28,29 to date, there are no studies on the expression of MMPs-7 and Ϫ26 in odontogenic lesions.…”

Expression of matrix metalloproteinase-26 promotes human glioma U251 cell invasion in vitro and in vivo

“…Most previous studies have focused on tumors derived from epithelia and have examined expression level of MMP-26 in normal and abnormal tissues (8,9,15,16,(33)(34)(35). MMP-26 may contribute to the local invasion of cancer cells since it is located at the leading edge of invading cells (21 Figure 8. Microvessel density analysis in subcutaneously transplanted tumors.…”

“…The elevated expression of MMP-26 is correlated with myometrial invasion of endometrial carcinoma (17,19). MMP-26 also contributes to the local depth of invasion in breast carcinoma, prostate carci-noma and esophageal squamous cell carcinoma (14,(20)(21)(22)(23)(24)(25)(26). The expression of MMP-26 seems to be located in the invading cells.…”