Journal Article

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

Hiroyuki Yamamoto, Akravit Vinitketkumnuen, Yasushi Adachi, Hiroaki Taniguchi, Tamaki Hirata, Nobuki Miyamoto, Katsuhiko Nosho, Arisa Imsumran, Masahiro Fujita, Masao Hosokawa, Yuji Hinoda and Kohzoh Imai

in Carcinogenesis

Volume 25, issue 12, pages 2353-2360
Published in print December 2004 | ISSN: 0143-3334
Published online December 2004 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgh270
Association of matrilysin-2 (MMP-26) expression with tumor progression and activation of MMP-9 in esophageal squamous cell carcinoma

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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 β-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 β-catenin expression and active MMP-9 activity, plays a key role in the progression of ESCC.

Keywords: ECM, extracellular matrix; ESCC, esophageal squamous cell carcinoma; MMP, matrix metalloproteinase; PBS, phosphate-buffered saline; RT–PCR, reverse transcriptase–polymerase chain reaction; TCF, T cell factor; pTNM, pathological tumor node metastasis

Journal Article.  4845 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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