scholarly journals CXCR3 mediates ascites-directed tumor cell migration and predicts poor outcome in ovarian cancer patients

Oncogenesis ◽  
2017 ◽  
Vol 6 (5) ◽  
pp. e331-e331 ◽  
Author(s):  
C Windmüller ◽  
D Zech ◽  
S Avril ◽  
M Boxberg ◽  
T Dawidek ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Migration ◽  
Tumor Cell ◽  
Cancer Patients ◽  
Tumor Cell Migration ◽  
Poor Outcome

scholarly journals SOX30 is a prognostic biomarker and chemotherapeutic indicator for advanced-stage ovarian cancer

2019 ◽  
Vol 26 (3) ◽  
pp. 303-319 ◽  
Author(s):  
Fei Han ◽  
Wen-bin Liu ◽  
Jian-jun Li ◽  
Ming-qian Zhang ◽  
Jun-tang Yang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Tumor Cell ◽  
Cancer Patients ◽  
Tumor Metastasis ◽  
Chromosomal Region ◽  
Migration And Invasion ◽  
Advanced Stage ◽  
Mesenchymal Transition ◽  
Tumor Cell Migration ◽  
E Cadherin

New potential biomarkers and therapeutic targets for ovarian cancer should be identified. The amplification in chromosomal region 5q31–5q35.3 exhibits the strongest correlation with overall survival (OS) of ovarian cancer. SOX30 coincidentally located at this chromosomal region has been determined as a new important tumor suppressor. However, the prognostic value, role and mechanism of SOX30 in ovarian cancer are unexplored. Here, we reveal that SOX30 is frequently overexpressed in ovarian cancer tissues and is associated with clinical stage and metastasis of ovarian cancer patients. High SOX30 expression predicts better OS and acts as an independent prognostic factor in advanced-stage patients, but is not associated with OS in early-stage patients. Based on the survival analyses, the advanced-stage patients with high SOX30 expression can receive platin- and/or taxol-based chemotherapy, whereas they should not receive chemotherapy containing gemcitabine or topotecan. Functionally, SOX30 strongly inhibits tumor cell migration and invasion in intro and suppresses tumor metastasis in vivo. SOX30 regulates some markers (E-CADHERIN, FIBRONECTIN, N-CADHERIN and VIMENTIN) and prevents the characteristics of epithelial–mesenchymal transition (EMT). SOX30 transcriptionally regulates the expression of E-CADHERIN, FIBRONECTIN and N-CADHERIN by binding to their promoters. Restoration of E-CADHERIN and/or N-CADHERIN when overexpressing SOX30 significantly reduces the anti-metastatic role of SOX30. Indeed, chemotherapy treatment containing platin or gemcitabine combined with SOX30 expression influences tumor cell metastasis and the survival of nude mice differently, which is closely associated with EMT. In conclusion, SOX30 antagonizes tumor metastasis by preventing EMT process that can be used to predict survival and incorporated into chemotherapeutics of advanced-stage ovarian cancer patients.

scholarly journals Neutrophil Granulocytes in Ovarian Cancer - Induction of Epithelial-To-Mesenchymal-Transition and Tumor Cell Migration

2016 ◽  
Vol 7 (5) ◽  
pp. 546-554 ◽  
Author(s):  
Christine Mayer ◽  
Silvia Darb-Esfahani ◽  
Anne-Sophie Meyer ◽  
Katrin Hübner ◽  
Joachim Rom ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Migration ◽  
Tumor Cell ◽  
Epithelial To Mesenchymal Transition ◽  
Neutrophil Granulocytes ◽  
Mesenchymal Transition ◽  
Tumor Cell Migration ◽  
Cancer Induction

scholarly journals Host and Tumor Factor XII Drive Ovarian Cancer Maintenance and Progression

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2384-2384
Author(s):  
Evi X Stavrou ◽  
Kara L. Bane ◽  
Peronne Joseph ◽  
Anil Belur Nagaraj ◽  
Analisa Difeo
Keyword(s):  
Ovarian Cancer ◽  
Cell Migration ◽  
Tumor Cell ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Ovarian Tumor ◽  
Low Grade ◽  
Factor Xii ◽  
Urokinase Plasminogen Activator Receptor ◽  
Tumor Cell Migration

Host and Tumor Factor XII Drive Ovarian Cancer Maintenance and Progression Introduction . Epithelial ovarian cancer (EOC) is the leading cause of cancer death in women.Effective strategies to treat this disease are lacking due to the complexity of pathways involved and the multitude of cells that contribute to EOC biology. To this end, coagulation factor XII (FXII) and its receptor urokinase plasminogen activator receptor (uPAR) represent very promising therapeutic targets because i) uPAR is overexpressed in more than 90% of ovarian cancer patients, ii) FXII has been shown to be upregulated in the peritoneum of EOC patients and promotes EOC dissemination and iii) FXII-uPAR signal and upregulate key neutrophil functions, recently linked to tumor growth and metastasis. Through analysis of the TCGA ovarian cancer patient cohort, we have found that FXII and uPAR are co-expressed in ovarian tumors and their overexpression is associated with decreased overall survival (Fig 1A-B). Given that FXII and uPAR can be produced by both the EOC tumor and the host, the contribution of each of these compartments which has not been examined to date needs to be explored. Thus, we asked if the FXII-uPAR axis in neutrophils and EOC cells synergistically influences tumor biology. Methods - Results. We utilized a tissue microarray to determine FXII and uPAR expression. Both FXII and uPAR were co-expressed in all major histologic subtypes of EOC tumors but not in normal ovarian epithelium (Fig C-D). We adopted a composite expression score system and found significantly increased expression of FXII and uPAR in high grade tumors compared to low grade (grade 1-2) tumors, independently of tumor subtype and stage (Fig 1C-D). Given prior reports that neutrophils are enriched in the ovarian tumor microenvironment (TME) and our findings that FXII-uPAR are integral to neutrophil activation, tumors were also examined for their neutrophil content. Invariably, as tumor grade advanced, Neutrophil Elastase expression significantly increased (data not shown). We next asked if neutrophils contribute to EOC tumor progression or their recruitment merely correlates with advanced disease. We found that in the presence of neutrophils, EOC cells migrate significantly faster (p<0.0001). Since enhanced tumor cell migration implies a pro-mesenchymal phenotype, we examined if neutrophils facilitate EOC cell epithelial-to-mesenchymal transition (EMT). Murine EOC cancer cells (ID8) were co-cultured with wild type (WT) neutrophils for 24 h; cells were harvested and used for immunoblotting and mRNA studies. We found that WT neutrophils significantly increased the expression of mesenchymal marker(s) vimentin and N-cadherin while they decreased the expression of E-cadherin, suggesting that neutrophils promote EMT of EOC cancer cells (Fig 1E). To investigate whether the FXII-uPAR axis contributed to neutrophil-induced EMT, we next co-cultured ID8 cells with neutrophils from tumor-bearing FXII deleted (F12-/-)mice. In ID8 cells co-cultured with F12-/-neutrophils, EOC induced EMT was blocked. Similarly, treatment with 2 peptide inhibitors that block the FXII-uPAR interaction (collectively termed, SMPAs), reversed the pro-invasive effects of both ID8 cells and WT neutrophils (Fig 1F). Next, in order to assess whether host FXII could contribute to EOC dissemination and progression we utilized WT, F12-/-, and uPAR deficient (Plaur-/-) mice for in vivo EOC tumor model. After orthotopic injection of ID8 EOC cells, WT mice exhibited faster rates of tumor development and ascitic fluid accumulation (13.4 ± 0.92 ml), relative to F12-/- (0.37 ± 0.26 ml) and Plaur-/- (0.5 ± 0.5 ml) mice (Fig 1G). Blinded examination of tumors showed significantly higher tumor burden in WT mice compared to F12-/-and Plaur-/- mice, with F12-/-mice exhibiting the highest degree of protection (Fig 1H). Conclusions . Our studies indicate three novel aspects: i) a direct crosstalk between ovarian cancer cells and neutrophils, that enhances tumor cell migration through FXII-uPAR signaling; ii) the presence of neutrophils in the TME induces EMT of cancer cells which is abolished when the FXII-uPAR interaction is inhibited and; iii) abrogation of the FXII-uPAR axis in EOC tumor cells and neutrophils, synergistically restricts the pro-invasive phenotype of ovarian tumor cells. Disclosures No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document