Matrilysin gene expression in sporadic and familial colorectal adenomas

Takeuchi, Nobumichi; Ichikawa, Yasushi; Ishikawa, Takashi; Momiyama, Nobuyoshi; Hasegawa, S.; Nagashima, Yoji; Miyazaki, Kaoru; Koshikawa, Naohiko; Mitsuhashi, Masato; Shimada, Hiroshi

doi:10.1002/(sici)1098-2744(199708)19:4<225::aid-mc2>3.0.co;2-b

Cited by 36 publications

(24 citation statements)

References 14 publications

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“…6 Thus, these data suggest that MMP-7 is involved in maintaining the patentability of the glandular lumen by digesting unknown non-ECM proteins in the lumen 4 and/or defending bacterial infections by activating defensin. 6 On the other hand, MMP-7 is overexpressed in human adenoma cells of the breast and colon, 7,8 as well as carcinoma cells in the human gastrointestinal, endometrial and lung adenocarcinomas. [9][10][11][12] Thus, MMP-7 is considered to contribute to early tumor development during carcinogenesis.…”

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confidence: 99%

Pericellular activation of proMMP-7 (promatrilysin-1) through interaction with CD151

Shiomi

Inoki

Kataoka

et al. 2005

Laboratory Investigation

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Matrix metalloproteinase-7 (MMP-7) (also known as matrilysin-1) is secreted as a proenzyme (proMMP-7) and plays a key role in the degradation of various extracellular matrix (ECM) and non-ECM molecules after activation. To identify the binding proteins related to proMMP-7 activation, a human lung cDNA library was screened by yeast two-hybrid system using proMMP-7 as bait. We identified a candidate molecule CD151, which is a member of the transmembrane 4 superfamily. Complex formation of proMMP-7 with CD151 was demonstrated by immunoprecipitation of the molecules from CaR-1 cells, a human rectal carcinoma cell line, expressing both proMMP-7 and CD151, and CD151 stable transfectants incubated with proMMP-7. Yeast twohybrid assays using deletion mutants of proMMP-7 and CD151 suggested an interaction between the propeptide of proMMP-7 and the COOH-terminal extracellular loop of CD151. The binding activity of 125 I-labeled proMMP-7 to CD151 on the cell membranes was shown with CD151 stable transfectants. Laser-scanning confocal microscopy demonstrated that proMMP-7 colocalizes with CD151 on the cell membranes of CD151 stable transfectants and CaR-1 cells. In situ zymography using crosslinked carboxymethylated transferrin, a substrate of MMP-7, demonstrated proteinase activity on and around CD151 stable transfectants and CaR-1 cells, while the activity was abolished by their treatment with MMP inhibitors, anti-MMP-7 antibody or anti-CD151 antibody. In human lung adenocarcinoma tissues, colocalization of MMP-7 and CD151 was demonstrated on the carcinoma cells. Metalloproteinase activity was present in these tissues and could be inhibited by antibodies to MMP-7 or CD151. These data demonstrate for the first time that proMMP-7 is captured and activated on the cell membranes through interaction with CD151, and suggest the possibility that similar to the MT1-MMP/MMP-2 system, MMP-7 is involved in the pericellular activation mechanism mediated by CD151, a crucial step in proteolysis on the cell membranes under various pathophysiological conditions including cancer invasion and metastasis.

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confidence: 99%

Pericellular activation of proMMP-7 (promatrilysin-1) through interaction with CD151

Shiomi

Inoki

Kataoka

et al. 2005

Laboratory Investigation

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“…34 This has been observed in adenomas or premalignant lesions of the intestine, stomach, prostate, breast and ovary. [51][52][53][54][55][56] We observed low levels of MMP7 in normal human lung epithelial cells, while the expression increased in premalignant and neoplastic cells. Using genetically manipulated animals, a definite role for MMP7 in early tumor development has been established.…”

Section: Discussionmentioning

confidence: 99%

Achaete-scute homolog-1 linked to remodeling and preneoplasia of pulmonary epithelium

Wang

Dakir

Naizhen

et al. 2007

Laboratory Investigation

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The basic helix-loop-helix protein achaete-scute homolog-1 (ASH1) is involved in lung neuroendocrine (NE) differentiation and tumor promotion in SV40 transgenic mice. Constitutive expression of human ASH-1 (hASH1) in mouse lung results in hyperplasia and remodeling that mimics bronchiolization of alveoli (BOA), a potentially premalignant lesion of human lung carcinomas. We now show that this is due to sustained cellular proliferation in terminal bronchioles and resistance to apoptosis. Throughout the airway epithelium the expression of anti-apoptotic Bcl-2 and c-Myb was increased and Akt/mTOR pathway activated. Moreover, the expression of matrix metalloproteases (MMPs) including MMP7 was specifically enhanced at the bronchiolo-alveolar duct junction and BOA suggesting that MMPs play a key role in this microenvironment during remodeling. We also detected MMP7 in 70% of human BOA lesions. Knockdown of hASH1 gene in human lung cancer cells in vitro suppressed growth by increasing apoptosis. We also show that forced expression of hASH1 in immortalized human bronchial epithelial cells decreases apoptosis. We conclude that the impact of hASH1 is not limited to cells with NE phenotype. Rather, constitutive expression of hASH1 in lung epithelium promotes remodeling through multiple pathways that are commonly activated during lung carcinogenesis. The collective results suggest a novel model of BOA formation via hASH1-induced suppression of the apoptotic pathway. Our study yields a promising new preclinical tool for chemoprevention of peripheral lung carcinomas. KEYWORDS: achaete-scute homolog 1; apoptosis; bronchiolization of alveoli; lung; mouse model; preneoplasia; proliferation Lung cancer is the leading cause of cancer deaths in both men and women in the United States. The 5-year survival rate has remained low (15%), because the disease is generally detected at advanced and disseminated stage. 1 Contributing to the late diagnosis is the fact that precursor lesions for most lung cancer types are poorly understood. We have previously shown that the deletion of achaete-scute homolog-1 (ASH1, ASCL1), a proneural transcription factor, highly expressed in lung neuroendocrine (NE) cancers leads to the absence of pulmonary NE cells (PNECs), potential progenitors for NE cancers. 2 Constitutive expression of human ASH1 (hASH1) in the airway epithelium, on the other hand, results in epithelial proliferation and metaplasia suggesting a preneoplastic phenotype.ASH1 belongs to a diverse family of transcriptional regulators involved in fetal development and cancer that utilize the evolutionarily conserved basic helix-loop-helix (bHLH) motif. 3 Murine ASH1 (mASH1) plays a critical role in the development of the brain and the diffuse NE system including adrenal medullary chromaffin cells, thyroid parafollicular C cells, glomus chief cells and PNECs, 2,4-8 potential progenitors for small cell lung cancer (SCLC). During neurogenesis mASH1 expression is confined to mitotically active precursors where it is involved in the early stages o...

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“…Unlike other matrix metalloproteinases whose expression correlates with the invasive and metastatic stages of tumor progression, matrilysin is also expressed in precancerous polyps suggesting a signi®cance prior to the onset of the invasive phenotype. Strikingly, matrilysin mRNA expression is found in over 90% of intestinal adenomas resulting from germline mutations in the APC gene in both human (Takeuchi et al, 1998) and mouse (Wilson et al, 1997). Metalloproteinases, and matrilysin in particular, are now recognized as contributing to tumor establishment and growth (Chambers and Matrisian, 1997).…”

Section: Introductionmentioning

confidence: 99%

The metalloproteinase matrilysin is a target of β-catenin transactivation in intestinal tumors

et al. 1999

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Matrilysin is a matrix metalloproteinase expressed in the tumor cells of greater than 80% of intestinal adenomas. The majority of these intestinal tumors are associated with the accumulation of b-catenin, a component of the cadherin adhesion complex and, through its association with the T Cell Factor (Tcf) DNA binding proteins, a regulator in the Wnt signal transduction pathway. In murine intestinal tumors, matrilysin transcripts show striking overlap with the accumulation of b-catenin protein. The matrilysin promoter is upregulated as much as 12-fold by b-catenin in colon tumor cell lines in a manner inversely proportional to the endogenous levels of b-catenin/Tcf complex and is dependent upon a single optimal Tcf-4 recognition site. Coexpression of the Ecadherin cytoplasmic domain blocked this induction and reduced basal promoter activity in every colon cancer cell line tested. Inactivation of the Tcf binding site increased promoter activity and overexpression of the Tcf factor, LEF-1, signi®cantly downregulated matrilysin promoter activity, suggesting that b-catenin transactivates the matrilysin promoter by virtue of its ability to abrogate Tcf-mediated repression. Because genetic ablation of matrilysin decreases tumor formation in multiple intestinal neoplasia (Min) mice, we propose that regulation of matrilysin production by b-catenin accumulation is a contributing factor to intestinal tumorigenesis.

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Matrilysin gene expression in sporadic and familial colorectal adenomas

Cited by 36 publications

References 14 publications

Pericellular activation of proMMP-7 (promatrilysin-1) through interaction with CD151

Pericellular activation of proMMP-7 (promatrilysin-1) through interaction with CD151

Achaete-scute homolog-1 linked to remodeling and preneoplasia of pulmonary epithelium

The metalloproteinase matrilysin is a target of β-catenin transactivation in intestinal tumors

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