Prognostic Significance of Extracellular Matrix Metalloproteinase Inducer and Matrix Metalloproteinase 2 in Epithelial Ovarian Cancer

Sillanpää, Sari; Anttila, Markku; Suhonen, Kirsi A.; Hämäläinen, K.; Turpeenniemi‐Hujanen, Taina; Puistola, Ulla; Tammi, Markku; Sironen, Reijo; Saarikoski, Seppo; Kosma, Veli‐Matti

doi:10.1159/000110426

Cited by 35 publications

(9 citation statements)

References 20 publications

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“…There are already papers showing that basigin is associated with the survival and progression of ovarian cancer, and is considered as a biomarker of poor outcome [39-41]. However, some results show that basigin is a significant indicator of a favorable prognosis of ovarian cancer [42,43]. In the present study, we described the relationship between basigin-2 expression and clinicopathological parameters of 146 cases of epithelial ovarian cancer with immunohistochemical analysis.…”

Section: Discussionmentioning

confidence: 80%

Basigin-2 is the predominant basigin isoform that promotes tumor cell migration and invasion and correlates with poor prognosis in epithelial ovarian cancer

Zhao

Wang

et al. 2013

J Transl Med

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BackgroundBasigin, which has four isoforms, has been demonstrated to be involved in progression of various human cancers. The aim of this study was to examine the prognostic value of basigin-2 protein expression in epithelial ovarian cancer. Furthermore, the function of basigin-2 in ovarian cancer was further investigated in cell culture models.MethodsImmunohistochemistry staining was performed to investigate basigin-2 expression in a total of 146 ovarian tissue specimens. Kaplan Meier analysis and Cox proportional hazards model were applied to assess the relationship between basigin-2 and progression-free survival (PFS) and overall survival (OS). Real-time PCR, RT-PCR and western blot were used to explore basigin-2, basigin-3 and basigin-4 expression in ovarian cancer cell lines and tissues. To evaluate possible contributions of basigin-2 to MMP secretion and cell migration and invasion, the overexpression vectors pcDNA3.1-basigin-2 and basigin-2 siRNA were transfected into HO-8910 and HO-8910 PM cells respectively.ResultsHigh basigin-2 expression was associated with lymph-vascular space involvement, lymph node metastasis and poor prognosis of epithelial ovarian cancer. Multivariate analyses indicated that basigin-2 positivity was an independent prognostic factor for PFS (P = 0.006) and OS (P = 0.019), respectively. Overexpression of basigin-2 increased the secretion of MMP-2/9 and cancer cell migration and invasion of HO-8910 cells, whereas knockdown of basigin-2 reduced active MMP-2/9 production, migration and invasion of HO-8910 PM cells.ConclusionsThe expression of basigin-2 might be an independent prognostic marker and basigin-2 inhibition would be a potential strategy for epithelial ovarian cancer patients, especially in inhibiting and preventing cancer cell invasion and metastasis.

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Section: Discussionmentioning

confidence: 80%

Basigin-2 is the predominant basigin isoform that promotes tumor cell migration and invasion and correlates with poor prognosis in epithelial ovarian cancer

Zhao

Wang

et al. 2013

J Transl Med

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“…Of note, only one study showed an increase in DFS with elevated CD147 expression [ 96 ]. There were 13 studies that did not have multivariate analysis data available ([ 26 , 57 , 60 , 62 , 71 , 72 , 77 , 82 , 84 , 91 , 92 , 99 , 100 ]; Supplementary Table 4). Of these, 8 had statistically significant univariate analysis revealing that elevated CD147 correlates with decreased DFS ([ 26 , 57 , 62 , 71 , 72 , 82 , 99 , 100 ]; Supplementary Table 4).…”

Section: Resultsmentioning

confidence: 99%

Prognostic Indications of Elevated MCT4 and CD147 across Cancer Types: A Meta-Analysis

Bovenzi

Hamilton

Tassone

et al. 2015

BioMed Research International

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Background. Metabolism in the tumor microenvironment can play a critical role in tumorigenesis and tumor aggression. Metabolic coupling may occur between tumor compartments; this phenomenon can be prognostically significant and may be conserved across tumor types. Monocarboxylate transporters (MCTs) play an integral role in cellular metabolism via lactate transport and have been implicated in metabolic synergy in tumors. The transporters MCT1 and MCT4 are regulated via expression of their chaperone, CD147. Methods. We conducted a meta-analysis of existing publications on the relationship between MCT1, MCT4, and CD147 expression and overall survival and disease-free survival in cancer, using hazard ratios derived via multivariate Cox regression analyses. Results. Increased MCT4 expressions in the tumor microenvironment, cancer cells, or stromal cells were all associated with decreased overall survival and decreased disease-free survival (p < 0.001 for all analyses). Increased CD147 expression in cancer cells was associated with decreased overall survival and disease-free survival (p < 0.0001 for both analyses). Few studies were available on MCT1 expression; MCT1 expression was not clearly associated with overall or disease-free survival. Conclusion. MCT4 and CD147 expression correlate with worse prognosis across many cancer types. These results warrant further investigation of these associations.

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“…Some studies have been published on the prognostic value of MMP2, MMP7 and TIMP2 in ovarian cancers, but it is still controversial. Most of them overexpressed in tumors, peritoneal implants or metastatic lesions that associated with poor outcome, but others predicted better survival [150–154]. Anyway, the effect of MMPs on the degradation of extracellular matrix to promote cell movement and migration is no doubt.…”

Section: Discussionmentioning

confidence: 99%

Nerve growth factor modulates the tumor cells migration in ovarian cancer through the WNT/β-catenin pathway

Cai

Zhao

et al. 2016

Oncotarget

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Nerve growth factor (NGF)/nerve growth factor receptors (NGFRs) axis and canonical WNT/β-catenin pathway have shown to play crucial roles in tumor initiation, progression and prognosis. But little did we know the relationship between them in modulation of tumor progress. In this report, we found that NGF/NGFRs and β-catenin were coexpression in ovarian cancer cell lines, and NGF can decrease the expression level of β-catenin and affect its activities, which may be related to the NGF-induced down-regulation of B-cell CLL/lymphoma 9-like (BCL9L, BCL9-2). Furthermore, NGF can also increase or decrease the downstream target gene expression levels of WNT/β-catenin depending on the cell types. Especially, we created a novel in vitro cell growth model based on a microfluidic device to intuitively observe the effects of NGF/NGFRs on the motility behaviors of ovarian cancer cells. The results showed that the migration area and maximum distance into three dimensional (3D) matrigel were decreased in CAOV3 and OVCAR3 cells, but increased in SKOV3 cells following the stimulation with NGF. In addition, we found that the cell colony area was down-regulated in CAOV3 cells, however, it was augmented in OVCAR3 cells after treatment with NGF. The inhibitors of NGF/NGFRs, such as Ro 08-2750, K252a and LM11A-31,can all block NGF-stimulated changes of gene expression or migratory behavior on ovarian cancer cells. The different results among ovarian cancer cells illustrated the heterogeneity and complexity of ovarian cancer. Collectively, our results suggested for the first time that NGF is functionally linked to β-catenin in the migration of human ovarian cancer cells, which may be a novel therapeutic perspective to prevent the spread of ovarian carcinomas by studying the interaction between NGF/NGFRs and canonical WNT/β-catenin signaling.

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Prognostic Significance of Extracellular Matrix Metalloproteinase Inducer and Matrix Metalloproteinase 2 in Epithelial Ovarian Cancer

Cited by 35 publications

References 20 publications

Basigin-2 is the predominant basigin isoform that promotes tumor cell migration and invasion and correlates with poor prognosis in epithelial ovarian cancer

Basigin-2 is the predominant basigin isoform that promotes tumor cell migration and invasion and correlates with poor prognosis in epithelial ovarian cancer

Prognostic Indications of Elevated MCT4 and CD147 across Cancer Types: A Meta-Analysis

Nerve growth factor modulates the tumor cells migration in ovarian cancer through the WNT/β-catenin pathway

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