Matrix Metalloproteinases Expression Correlates with Survival in Patients with Esophageal Squamous Cell Carcinoma

Gu, Zhengtao; Li, Jiyou; Li, Ming; Gu, Jin; Shi, Xianliang; Ke, Yang; Chen, Ke-Neng

doi:10.1111/j.1572-0241.2005.50018.x

Cited by 85 publications

(73 citation statements)

References 25 publications

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“…Houldsworth et al (27) identified an association between MET and EC, while Gu et al (28) showed that MMP9 affected the survival of patients with this disease. PDGFA was detected in EC by Wong et al (29) and Aoki et al (30) suggested that SERPINE1 may be a potentially important index for the prediction of post-operative illness.…”

Section: Discussionmentioning

confidence: 99%

Expression of MMP9, SERPINE1 and miR-134 as prognostic factors in esophageal cancer

et al. 2016

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Abstract. Esophageal cancer (EC) is a malignant tumor with a typically poor prognosis for patients. It is well known that certain microRNA (miRNA/miR) genes can regulate other genes responsible for carcinogenesis. In the present study, a group of these genes (miR-21, miR-134, miR-205 and miR-495) and genes connected with cancer-related pathways (MET, MMP9, PDGFA and SERPINE1) were chosen for analysis in order to find a potential correlation between their expression and the clinicopathological factors of EC. Esophageal tumors and adjacent non-cancerous tissue specimens were collected from a total of 63 patients and embedded in paraffin. Commercial arrays were used on KYSE-30, KYSE-150 and KYSE-270 EC cell lines in order to find genes of different expression profiles compared with those acquired from the control Het-1A cell line. Quantitative polymerase chain reaction was used on formalin-fixed, paraffin-embedded samples in order to analyze the expression of the genes chosen in the earlier step. The results were analyzed by the Kruskal-Wallis and Mann-Whitney U tests, Spearman's rank correlation coefficient, Kaplan-Meier methods and the long-rank test. Only miR-495 was not expressed in the analyzed samples. The expression of MMP9 and SERPINE1 was significantly coefficient with age range (P=0.011 and P=0.044, respectively) according to the Kruskal-Wallis test. The Spearman's rank-order correlation measurement showed that there was a coefficient correlation between age and miR-134 expression. The same measurement demonstrated a correlation between age range and MMP9 expression. The expression of miR-134 and MMP9 were also found to be correlated. In all cases, a value of P<0.049 was recorded. Overall, the present study demonstrated that MMP9, SERPINE1 and miR-134 were the most prognostic genes in Caucasian patients with EC.

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Section: Discussionmentioning

confidence: 99%

Expression of MMP9, SERPINE1 and miR-134 as prognostic factors in esophageal cancer

et al. 2016

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“…MMP-2 and MMP-9 activation has been proposed to be critical for carcinoma progression since the proteolytic ability of type IV collagen is associated with cancer metastatic ability (Liotta et al 1980(Liotta et al , 1991. Several reports have indicated that MMPs are associated with the malignant potential of esophageal cancer (Koyama et al 2000;Polette et al 2004;Samantaray et al 2004;Gu et al 2005). Interestingly, Kim et al (1998) demonstrated that MMP-9 activity, and not MMP-2 activity, could significantly affect tumor intravasation into blood vessels by degrading the basement membrane.…”

Section: The Combination Of Egfr Overexpression Htert Activation Anmentioning

confidence: 99%

The functional interplay between EGFR overexpression, hTERT activation, and p53 mutation in esophageal epithelial cells with activation of stromal fibroblasts induces tumor development, invasion, and differentiation

Okawa¹,

Michaylira²,

Kalabis³

et al. 2007

Genes Dev.

159

161

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Esophageal cancer is a prototypic squamous cell cancer that carries a poor prognosis, primarily due to presentation at advanced stages. We used human esophageal epithelial cells as a platform to recapitulate esophageal squamous cell cancer, thereby providing insights into the molecular pathogenesis of squamous cell cancers in general. This was achieved through the retroviral-mediated transduction into normal, primary human esophageal epithelial cells of epidermal growth factor receptor (EGFR), the catalytic subunit of human telomerase (hTERT), and p53 R175H, genes that are frequently altered in human esophageal squamous cell cancer. These cells demonstrated increased migration and invasion when compared with control cells. When these genetically altered cells were placed within the in vivo-like context of an organotypic three-dimensional (3D) culture system, the cells formed a high-grade dysplastic epithelium with malignant cells invading into the stromal extracellular matrix (ECM). The invasive phenotype was in part modulated by the activation of matrix metalloproteinase-9 (MMP-9). Using pharmacological and genetic approaches to decrease MMP-9, invasion into the underlying ECM could be suppressed partially. In addition, tumor differentiation was influenced by the type of fibroblasts within the stromal ECM. To that end, fetal esophageal fibroblasts fostered a microenvironment conducive to poorly differentiated invading tumor cells, whereas fetal skin fibroblasts supported a well-differentiated tumor as illustrated by keratin "pearl" formation, a hallmark feature of well-differentiated squamous cell cancers. When inducible AKT was introduced into fetal skin esophageal fibroblasts, a more invasive, less-differentiated esophageal cancer phenotype was achieved. Invasion into the stromal ECM was attenuated by genetic knockdown of AKT1 as well as AKT2. Taken together, alterations in key oncogenes and tumor suppressor genes in esophageal epithelial cells, the composition and activation of fibroblasts, and the components of the ECM conspire to regulate the physical and biological properties of the stroma.[Keywords: Cell migration and invasion; tumor microenvironment; EGFR; p53; MMP-9; AKT] Supplemental material is available at http://www.genesdev.org. Received February 22, 2007; revised version accepted September 5, 2007. 8 These authors contributed equally to this work. 9Corresponding author. E-MAIL anil2@mail.med.upenn.edu; FAX (215) 573-5412. Article is online at http://www.genesdev.org/cgi

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“…The first step of tumor development and metastasis is the proteolysis of microvessel basement membranes and invasion of endothelium. The migration of tumor cells is associated with the degradation of the extracellular matrix (ECM) [19]. The ECM is a dynamic structure composed of various macromolecules such as collagen, fibronectin, laminin and proteoglycans of connective tissue.…”

Section: Matrix Metalloproteinases (Mmps)mentioning

confidence: 99%

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

Groblewska

Siewko

Mroczko

et al. 2012

Folia Histochem Cytobiol.

169

108

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Esophageal cancer (EC) is one of the most aggressive malignant tumors of the gastrointestinal tract. There are two distinct histological types of EC: esophageal squamous cell carcinoma and adenocarcinoma of the esophagus. Etiologic factors and the patterns of incidence of both subtypes are different. Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) play an important role in esophageal carcinogenesis. Gellatinases MMP-2 and MMP-9 are able to degrade collagen IV from basement membranes and extracellular matrix which is related to tumor progression, including invasion, metastasis, growth and angiogenesis. It has been shown that increased expression of MMPs plays a crucial role in the development of several human malignancies, including esophageal cancer. The activity of MMPs is regulated by their endogenous natural inhibitors (TIMPs). Among these, the roles of TIMP-1 and TIMP-2 in EC development, tumor progression and formation of metastases have been most extensively characterized and best recognized.

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Matrix Metalloproteinases Expression Correlates with Survival in Patients with Esophageal Squamous Cell Carcinoma

Cited by 85 publications

References 25 publications

Expression of MMP9, SERPINE1 and miR-134 as prognostic factors in esophageal cancer

Expression of MMP9, SERPINE1 and miR-134 as prognostic factors in esophageal cancer

The functional interplay between EGFR overexpression, hTERT activation, and p53 mutation in esophageal epithelial cells with activation of stromal fibroblasts induces tumor development, invasion, and differentiation

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

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