Activation of c‐Met (hepatocyte growth factor receptor) in human gastric cancer tissue

Inoué, Takao; Kataoka, Hiroaki; Goto, Kouichiro; Nagaike, Koki; Igami, Ko; Naka, Daiji; Kitamura, Naomi; Miyazawa, Keiji

doi:10.1111/j.1349-7006.2004.tb02185.x

Cited by 72 publications

(72 citation statements)

References 27 publications

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“…Moreover, p-MET staining is more convenient compared with MET FISH and may act as a substitute method for choosing patients for anti-MET treatment. To date, several studies have evaluated p-MET expression in gastric cancer (36)(37)(38)(39), and the results were inconsistent. The p-MET-positive rate of 6% (8/134) observed in our study is similar to the rate reported by Janjigian and colleagues, who also used the same antibody that recognizes p-MET at Y1234/1235 (37).…”

Section: Discussionmentioning

confidence: 99%

Tumor MET Expression and Gene Amplification in Chinese Patients with Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Cancer

Peng

Gao

et al. 2015

Molecular Cancer Therapeutics

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MET and its sole ligand, hepatocyte growth factor (HGF), are promising targets in gastric and gastroesophageal junction cancer. We evaluated whether MET protein expression or MET gene amplification is prognostic for overall survival (OS) in Chinese patients with advanced gastric or gastroesophageal junction cancer. Archival formalin-fixed, paraffin-embedded tumor samples from patients with unresectable locally advanced or metastatic gastric or gastroesophageal junction cancer enrolled in clinical trials at Peking University Cancer Hospital from 2008 to 2010 were assessed for MET and phospho-MET (p-MET) expression by immunohistochemistry and MET amplification by FISH. MET-positive expression was defined as membrane protein staining in !25% of tumor cells. MET amplification was defined as MET:centromere 7 ratio >2.0. We tested the association of MET status with clinical characteristics and OS, and also evaluated the association between expression and amplification. One hundred sixty-eight patients were eligible. Of the evaluable samples, 53 of 137 (39%) were MET positive, eight of 134 (6%) were p-MET positive, and eight of 113 (7%) were MET amplified. Neither MET expression nor MET amplification were associated with clinical characteristics, except Lauren classification (P ¼ 0.04); MET amplification was associated with diffuse type. No significant OS difference was observed between MET-positive and MET-negative populations, regardless of first-line chemotherapy received. In 95 evaluable patients, MET expression was significantly associated with MET amplification (P < 0.001); all MET-amplified tumor samples showed some MET expression. In 96 evaluable patients, p-MET positivity was significantly associated with MET amplification (P < 0.001). Further evaluation in larger and independent sample sets is warranted to confirm our findings.

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Section: Discussionmentioning

confidence: 99%

Tumor MET Expression and Gene Amplification in Chinese Patients with Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Cancer

Peng

Gao

et al. 2015

Molecular Cancer Therapeutics

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“…11,23,28 In human gastric adenocarcinoma tissues, the in situ tyrosine phosphorylation of Met was detected in poorly differentiated adenocarcinoma, including in the invasion front, whereas Met was only weakly phosphorylated in a normal gastric mucosa even though Met was expressed. 29 Likewise, the Met receptor was in situ tyrosine-phosphorylated in invasive carcinomas in mice, whereas the inhibition of Met tyrosine phosphorylation was associated with the suppression of the invasive behavior. 30 These results indicate that the in situ activation of Met is associated with the invasive and metastatic progression of cancers.…”

Section: Hgf and Met: Brief Backgroundmentioning

confidence: 99%

Hepatocyte growth factor and the Met system as a mediator of tumor–stromal interactions

Matsumoto

Nakamura

2006

Intl Journal of Cancer

200

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Crosstalk between carcinoma cells and host stromal cells such as fibroblasts has a great deal of influence on the invasive and metastatic behavior of cancer cells. The oncogenic action of fibroblasts has been demonstrated through genetic alterations that occur specifically in fibroblasts. Hepatocyte growth factor (HGF), a ligand for the Met receptor tyrosine kinase, plays a definitive role, particularly in the progression to invasive and metastatic cancers, predominantly as a stroma-derived paracrine mediator. Many types of cancer cells secrete molecules that enhance HGF production in fibroblasts, while fibroblast-derived HGF, in turn, is a potent stimulator of the invasion of cancer cells. Fibroblast-specific genetic alterations leading to an overexpression of HGF are associated with the development of epithelial neoplasia and invasive carcinoma. Strategies for targeting the HGF-Met axis are being pursued, in attempts to block the malignant behavior of cancers. In normal tissues, the HGF-Met axis plays diverse roles in organogenesis and in wound healing. The simile that ''cancer is a never-healing wound'' appears to be pertinent here. ' 2006 Wiley-Liss, Inc.

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“…Anti-phospho-MET rabbit polyclonal antibody was prepared previously. (15) MET kinase specific inhibitor SU11274 [(3Z)-N-(3-chlorophenyl)-3-({3,5-dimethyl-4-[(4-methylpiperazin-1-yl)carbonyl]-1H-pyrrol-2-yl} methylene)-N-methyl-2-oxoindoline-5-sulfonamide] was purchased from Selleck Chemicals (Houston, TX, USA).…”

Section: Methodsmentioning

confidence: 99%

Regulation of microRNA expression by hepatocyte growth factor in human head and neck squamous cell carcinoma

et al. 2011

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Hepatocyte growth factor (HGF) is a multifunctional molecule that acts as mitogen, motogen, and ⁄ or morphogen in a variety of cells. MET, a specific receptor tyrosine kinase for HGF, is upregulated in various tumors including squamous cell carcinoma of the human head and neck (HNSCC), but how HGF affects the expression of downstream functional genes has not yet been elucidated in detail. In the present study, we examined the expression of micro-RNA (miRNA), non-coding small RNA that regulate cell proliferation and functions by interfering with the translation of target mRNA, with or without HGF stimulation in HNSCC cell line HSC3. Among several miRNAs, in which the expression was altered after HGF stimulation, we focused on miR-200c and miR-27b, both of which were drastically downregulated after HGF stimulation. Expression of ZEB1, a target mRNA for miR-200c, was upregulated 3 and 6 h after HGF stimulation, and that of E-cadherin, a downstream molecule of ZEB1, was downregulated 12 h after HGF stimulation. Expression of ST14 ⁄ matriptase, an enzyme for extracellular matrix (ECM) degradation and HGF activation and a target mRNA for miR-27b, was drastically upregulated in the protein level after HGF stimulation, although it was not statistically altered in the mRNA level. These results suggest that miR-200c and miR-27b downregulated by HGF might play an important role in epithelialmesenchymal transition mediated by ZEB1 ⁄ E-cadherin and ECM degradation and HGF autoactivation mediated by ST14 ⁄ matriptase, respectively. Altered expression of miRNA directly regulated by HGF might contribute enhanced progressive and invasive characteristics of HNSCC by regulating the translation of HGF-induced functional molecules. (Cancer Sci 2011; 102: 2164-2171 S quamous cell carcinoma (SCC) is a common malignant tumor in the head and neck and constitutes 90% of malignancies in these regions.(1,2) The incidence and mortality of head and neck SCC (HNSCC) is increasing despite intense efforts, and its 5-year survival rate is <50%.(2,3) Several growth factors are considered to contribute to the carcinogenesis and progression of HNSCC.(2) One of these factors, hepatocyte growth factor (HGF), is a multifunctional growth factor that acts as mitogen, motogen and ⁄ or morphogen in a variety of cells including squamous epithelial cells.(4-6) MET, a specific receptor tyrosine kinase for HGF, is upregulated in various tumors including human HNSCC, and its signal transduction to the nucleus induces the expression of genes involving the progressive and invasive characteristics of HNSCC.(5-7) However, how HGF affects downstream functional gene expression has not yet been elucidated in detail.MicroRNA (miRNA) are non-coding small RNA (21-25 nucleotides) that regulate post-transcriptional gene expression by interfering with the translation of target mRNA. (8,9) One miRNA might regulate the expression of several genes and over one-third of all protein-coding genes might be under translational control by miRNA. (9) MiRNA are involved in a variety ...

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Activation of c‐Met (hepatocyte growth factor receptor) in human gastric cancer tissue

Cited by 72 publications

References 27 publications

Tumor MET Expression and Gene Amplification in Chinese Patients with Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Cancer

Tumor MET Expression and Gene Amplification in Chinese Patients with Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Cancer

Hepatocyte growth factor and the Met system as a mediator of tumor–stromal interactions

Regulation of microRNA expression by hepatocyte growth factor in human head and neck squamous cell carcinoma

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