Prognostic significance of cyclooxygenase‐2 and DNA topoisomerase IIα expression in oral carcinoma

Sakurai, Kazuo; Urade, Masahiro; Noguchi, Kazuma; Hashitani, Susumu; Takaoka, Kazuki; Segawa, Emi; Kishimoto, Hiroyuki

doi:10.1002/hed.20627

Cited by 24 publications

(33 citation statements)

References 34 publications

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“…The current study demonstrated the expression of COX-2 in the odontogenic epithelium of dentigerous cyst and ameloblastoma. COX-2 is upregulated in a wide variety of human tumors including oral cancer (12,(23)(24)(25). The precise contribution of COX-2 to neoplastic growth has not been elucidated (26).…”

Section: Discussionmentioning

confidence: 99%

Odontogenic epithelial proliferation is correlated with COX-2 expression in dentigerous cyst and ameloblastoma

Alsaegh

Matsumoto

Taniguchi

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. Investigation of cyclooxygenase (COX)-2 in dentigerous cyst and ameloblastoma may help to improve understanding of the nature and behavior of odontogenic cysts and tumors, and in addition may eventually represent a definitive target for a pharmacological approach in the management of these lesions. The aim of this study was to evaluate COX-2 expression and its correlation with the proliferation of odontogenic epithelium in these lesions. Dentigerous cysts (n=16) and ameloblastomas (n=17) were evaluated. Detection of Ki-67 and COX-2 protein expression was conducted by immunohistochemistry. Data were statistically analyzed using Mann-Whitney U test and Spearman's rank correlation coefficient. No significant differences were found in the expression of Ki-67 and COX-2 between dentigerous cysts and ameloblastomas (P>0.05). A significant positive correlation (P= 0.018) and highly significant positive correlation (P=0.004) were found between Ki-67 and COX-2 expression in the odontogenic epithelium of dentigerous cyst and ameloblastoma, respectively. COX-2 was expressed in the odontogenic epithelium of dentigerous cyst and ameloblastoma. It may contribute to local extension of these lesions by increasing the proliferation of their odontogenic epithelial cells.

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Section: Discussionmentioning

confidence: 99%

Odontogenic epithelial proliferation is correlated with COX-2 expression in dentigerous cyst and ameloblastoma

Alsaegh

Matsumoto

Taniguchi

et al. 2016

Experimental and Therapeutic Medicine

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“…Moreover, opinions regarding the correlation between COX-2 expression and the histologic grade of oral cancer are highly conflicting; many authors report a progressive increase of COX-2 expression from normal oral mucosa towards invasive carcinoma [39,[41][42][43], others report an higher COX-2 expression in premalignant lesion than in malignancies [4,6,[44][45], while others report the lack of correlation between COX-2 level and tumor stage or grade [7,46].…”

Section: Discussionmentioning

confidence: 99%

Expression of cyclooxygenase-1 and cyclooxygenase-2 in normal and pathological human oral mucosa.

Mauro

Lipari²,

Leone

et al. 2011

Folia Histochem Cytobiol.

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Cyclooxigenase (COX) is the rate-limiting enzyme for the conversion of arachidonic acid (AA) to prostaglandins (PGs). Two isoforms of COX have been identified: COX-1 is constitutively expressed in many cells and is involved in cell homeostasis, angiogenesis and cell-cell signalling; COX-2 is not expressed in normal condition however it is strongly expressed in inflammation. The oral cavity is costantly exposed to physical and chemical trauma that could lead to mucosal reactions such as hyperplasia, dysplasia and cancer. Early diagnosis is the most important issue to address for a positive outcome of oral cancer; therefore it would be useful to identify molecular markers whose expression is associated with the various stages of oral cancer progression. Since COX enzyme has been involved, with different mechanisms, in the development and progression of malignancies we decided to investigate the expression and localization of COX-1 and COX-2 in normal human oral mucosa and three different pathologies (hyperplasia, dysplasia and carcinoma) by immunohistochemistry and RT-PCR. COX-1 mRNA and protein have been detected already in normal oral mucosa and their expression progressively increases from normal samples towards hyperplasia, dysplasia and finally carcinoma. On the contrary, COX-2 is not expressed in the normal tissue, starts to be expressed in hyperplasia, reaches the maximum activation in dysplasia and then starts to be downregulated in carcinoma.

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“…However, few studies have been reported concerning the relation between COX-2 expression and metastasis of tumor cells in head and neck carcinoma (16)(17)(18). The significance of COX-2 expression in relation to tumor cell migration, invasion and metastasis of head and neck carcinoma is still poorly understood.…”

Section: Discussionmentioning

confidence: 99%

“…Inhibitory effect of COX-2 siRNA treatment on PGE 2 production and cell motility. (A) PGE 2 immunoassay was performed as indicated in a protocol of prostaglandin E2 EIA kit (Cayman Chemical) as described previously (16). (B) Wound healing assay was performed using 60-mm fibronectin-coated dishes (Asahi Techno Glass Co.) and (C) invasion assay was carried out using BioCoat Matrigel Invasion Chambers (Becton-Dickinson Labware) as described previously (11 we next examined the inhibitory effect on COX-2 in vivo.…”

Section: Suppression Of Cox-2 Expression In Kb/cox-2 Cells By Treatmementioning

confidence: 99%

Promotion of hematogenous metastatic potentials in human KB carcinoma cells with overexpression of cyclooxygenase-2

Segawa

Kishimoto²,

Takaoka³

et al. 2010

Oncol Rep

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Abstract.To understand the role of cyclooxygenase (COX)-2 in metastatic potential of oral cancer, COX-2 overexpressing KB/COX-2 cells were inoculated orthotopically into the masseter muscle or injected into the left cardiac ventricle of nude mice. KB/COX-2 showed about 4-fold increase of COX-2 protein expression as compared to KB/Neo which was a mock transfected control. In orthotopic inoculation, metastasis to the regional lymph nodes occurred in 2 out of 15 mice, and metastasis to the lung in 3 out of 15 mice. On the other hand, in intra-cardiac injection, hematogenous metastasis to the lung and bone occurred in 8 out of 10 mice in KB/COX-2, but no metastasis occurred except for only one metastasis to the femur bone out of 10 mice in KB/Neo. Treatment of KB/COX-2 with COX-2 small interfering RNA (siRNA) inhibited the colony formation but not cell growth in vitro, and suppressed tumorigenicity and hematogenous metastasis in nude mice. When expression of adhesion molecules such as E-cadherin, ·-catenin, ß-catenin and CD44 was examined, there was no difference in ·-and ß-catenin between the cells. However, expression of E-cadherin was detected in KB/Neo, but not in KB/COX-2. In contrast, expression of CD44 was markedly increased in KB/COX-2 as compared to KB/Neo. Treatment with COX-2 siRNA resulted in suppression of CD44 expression and detectable expression of E-cadherin in KB/COX-2. These findings suggested that overexpression of COX-2 increased hematogenous metastasis, at least in KB cells, via down-regulating E-cadherin and up-regulating CD44 expression. IntroductionCyclooxygenase (COX)-2 is an enzyme induced by mitogens, cytokines and growth factors of epithelial cells and plays an important role in prostaglandin (PG) production. Overexpression of COX-2 has been reported in a variety of cancers (1-4) including head and neck cancer (5-8). Recently, a human colon cancer cell line transfected with a COX-2 expression vector acquired increased invasiveness and metastatic potential with activation of matrix metalloproteinase (MMP) (9). A correlation between COX-2 overexpression and hematogenous metastasis of colorectal cancer was also demonstrated (10). These findings suggest that COX-2 overexpression is involved in colon cancer metastasis. In head and neck cancer, however, the significance of COX-2 overexpression in metastasis is poorly understood.We have already shown that KB/COX-2, which was established by stable transfection with full length COX-2 cDNA to human KB carcinoma cells, showed elevated PGE 2 production, cell migration and invasion as compared to mock transfected control, KB/Neo. Furthermore, it was found that KB/COX-2 increased tumorigenicity, tumor growth and local tumor invasion in nude mice. These effects were apparently modulated by up-regulation of MMPs and Rho family small guanosine triphosphatases (GTPases) and down-regulation of tissue inhibitor of metalloproteinase (TIMP) activities (11).The aim of this study was to investigate the metastatic potential in nude mice using KB/COX-2. In additio...

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Prognostic significance of cyclooxygenase‐2 and DNA topoisomerase IIα expression in oral carcinoma

Abstract: Expression of COX-2 and DNA-Topo IIalpha were related to lymph node metastasis, cell proliferative activity, and overall 5-year survival rate in oral carcinoma. These enzymes may therefore be valuable diagnostic and prognostic indices in oral carcinoma.

Cited by 24 publications

References 34 publications

Odontogenic epithelial proliferation is correlated with COX-2 expression in dentigerous cyst and ameloblastoma

Odontogenic epithelial proliferation is correlated with COX-2 expression in dentigerous cyst and ameloblastoma

Expression of cyclooxygenase-1 and cyclooxygenase-2 in normal and pathological human oral mucosa.

Promotion of hematogenous metastatic potentials in human KB carcinoma cells with overexpression of cyclooxygenase-2

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