Inhibition of invasion and metastasis in oral cancer by targeting urokinase-type plasminogen activator receptor

Nozaki, Shinichi; Endo, Yuichi; Nakahara, Hirokazu; Yoshizawa, Kunio; Hashiba, Yukari; Kawashiri, Shin‐ya; Tanaka, Akira; Nakagawa, Kiyomasa; Matsuoka, Yoshihiko; Kogo, Mikihiko; Yamamoto, Etsuhide

doi:10.1016/j.oraloncology.2005.05.013

Cited by 32 publications

(23 citation statements)

References 28 publications

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“…Seven of the nine showed significant inhibition by a pooled t test. Among these nine completely blocked genes were arachidonate 5-lipoxygenaseactivating protein (Alox5ap), urokinase plasminogen activator (Plaur) and osteopontin (Spp1/Opn), already shown to be involved in driving tumor promotion and progression (29)(30)(31)(32). Despite the P value of 0.062, the inhibition of TPA-induced Opn mRNA expression by TAM67 was confirmed by quantitative PCR (Table 1), showing about 15-fold inhibition.…”

Section: Resultsmentioning

confidence: 96%

Dominant-Negative Activator Protein 1 (TAM67) Targets Cyclooxygenase-2 and Osteopontin under Conditions in which It Specifically Inhibits Tumorigenesis

et al. 2007

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Activation of activator protein 1 (AP-1) and nuclear factor KB (NFKB)-dependent transcription is required for tumor promotion in cell culture models and transgenic mice. Dominant-negative c-Jun (TAM67) blocks AP-1 activation by dimerizing with Jun or Fos family proteins and blocks NFKB activation by interacting with NFKB p65. Two-stage [7,12-dimethylbenz(a)anthracene (DMBA)/12-O -tetradecanoylphorbol-13-acetate (TPA)] skin carcinogenesis experiments in a model relevant to human cancer risk, transgenic mice expressing human papillomavirus 16 E7 oncogene (K14-HPV16-E7), show E7-enhanced tumor promotion. A cross to K14-TAM67-expressing mice results in dramatic inhibition of tumor promoter-induced AP-1 luciferase reporter activation and papillomagenesis. Epithelial specific TAM67 expression inhibits tumorigenesis without affecting TPA-or E7-induced hyperproliferation of the skin. Thus, the mouse model enriches for TAM67 targets relevant to tumorigenesis rather than to general cell proliferation or hyperplasia, implicating a subset of AP-1-and/or NFKB-dependent genes. The aim of the present study was to identify target genes responsible for TAM67 inhibition of DMBA-TPA-induced tumorigenesis. Microarray expression analysis of epidermal tissues revealed small sets of genes in which expression is both up-regulated by tumor promoter and down-regulated by TAM67. Among these, cyclooxygenase-2 (Cox-2/Ptgs2) and osteopontin (Opn/Spp1) are known to be functionally significant in driving carcinogenesis. Results identify both Cox-2 and Opn as transcriptional targets of TAM67 with CRE, but not NFKB sites important in the Cox-2 promoter and an AP-1 site important in the Opn promoter. [Cancer Res 2007;67(6):2430-8]

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Section: Resultsmentioning

confidence: 96%

Dominant-Negative Activator Protein 1 (TAM67) Targets Cyclooxygenase-2 and Osteopontin under Conditions in which It Specifically Inhibits Tumorigenesis

et al. 2007

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“…It is involved in localizing and promoting cell-surface plasminogen activation, plasmin formation and localized degradation of the extracellular matrix. 42 Overexpression of UPAR has been found in many cancers 23,[43][44][45][46] including pancreatic cancer, and contributes to tumor invasion and metastasis. 24,25 Recent studies by Ellis and colleagues have shown that pancreatic metastatic disease is dependent upon the UPA/ UPAR system, and that system activation and subsequent metastases is (i) mediated by insulin growth factor-1, hepatocyte growth (Table I).…”

Section: Discussionmentioning

confidence: 99%

Accurate discrimination of pancreatic ductal adenocarcinoma and chronic pancreatitis using multimarker expression data and samples obtained by minimally invasive fine needle aspiration

Chen

Zheng

Robbins

et al. 2007

Intl Journal of Cancer

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To augment cytological diagnosis of pancreatic ductal adenocarcinoma (PDAC) in tissue samples obtained by minimally invasive endoscopic ultrasound-guided fine needle aspiration, we investigated whether a small set of molecular markers could accurately distinguish PDAC from chronic pancreatitis (CP). Expression levels of 29 genes were first determined by quantitative real-time RT-PCR in a training set of tissues in which the final diagnosis was PDAC (n 5 20) or CP (n 5 10). Using receiver operator characteristic curve analysis, we determined that the single gene with the highest diagnostic accuracy for discrimination of CP vs. PDAC in the training study was urokinase plasminogen activator receptor (UPAR; AUC value 5 0.895, 95% CI 5 0.728-0.976). In the set of test tissues (n 5 14), the accuracy of UPAR decreased to 79%. However, we observed that the addition of 6 genes (EPCAM2, MAL2, CEA5, CEA6, MSLN and TRIM29; referred to as the 6-gene classifier) to UPAR resulted in high accuracy in both training and testing sets. Excluding 3 samples (out of 44; 7%) for which results of the UPAR/6-gene classifier were ''undefined,'' the accuracy of the UPAR/6-gene classifier was 100% in training samples (n 5 29), 92% in 12 test samples (p 5 0.004 that results were randomly generated; p 5 0.046 that the UPAR/6-gene classifier was comparable to UPAR alone; v 2 test), 100% in 3 samples for which the initial cytological diagnosis was ''suspicious'' and 98% (40/41) overall. Our results provide evidence that molecular marker expression data can be used to augment cytological analysis. ' 2006 Wiley-Liss, Inc.Key words: chronic pancreatitis; pancreatic ductal adenocarcinoma; urokinase plasminogen activator receptor; diagnostic accuracy Although the incidence of pancreatic ductal adenocarcinoma (PDAC) is only 1-2% and relatively low compared to other cancers, nearly all patients die from PDAC within 1-2 years.

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“…Cell culture was performed as described previously by Nozaki et al (12). Cell lines were derived from OSCC with the following grades of invasiveness, according to the Yamamoto-Kohama criteria (9): HSC-4 and OSC-20 cells of grade 3 described as mildly invasive; OSC-19 and OTC-04 of grade 4C described as highly invasive; HOC313 and TSU of grade 4D described as most highly invasive.…”

Section: Specimensmentioning

confidence: 99%

Expression of urokinase-type plasminogen activator/urokinase-type plasminogen activator receptor and maspin in oral squamous cell carcinoma: Association with mode of invasion and clinicopathological factors

Yoshizawa

Nozaki²,

Kitahara³

et al. 2011

Oncol Rep

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Inhibition of invasion and metastasis in oral cancer by targeting urokinase-type plasminogen activator receptor

Cited by 32 publications

References 28 publications

Dominant-Negative Activator Protein 1 (TAM67) Targets Cyclooxygenase-2 and Osteopontin under Conditions in which It Specifically Inhibits Tumorigenesis

Dominant-Negative Activator Protein 1 (TAM67) Targets Cyclooxygenase-2 and Osteopontin under Conditions in which It Specifically Inhibits Tumorigenesis

Accurate discrimination of pancreatic ductal adenocarcinoma and chronic pancreatitis using multimarker expression data and samples obtained by minimally invasive fine needle aspiration

Expression of urokinase-type plasminogen activator/urokinase-type plasminogen activator receptor and maspin in oral squamous cell carcinoma: Association with mode of invasion and clinicopathological factors

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