scholarly journals Epiphycan Predicts Poor Outcomes and Promotes Metastasis in Ovarian Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Lu Deng ◽  
Dandan Wang ◽  
Shouzhen Chen ◽  
Weiguo Hu ◽  
Ru Zhang
Keyword(s):  
Ovarian Cancer ◽  
Molecular Mechanisms ◽  
Ovarian Cancer Cell Line ◽  
Cancer Cell Line ◽  
Scratch Test ◽  
The Cancer Genome Atlas ◽  
Primary Ovarian Cancer ◽  
Skov3 Cells ◽  
Cancer Genome Atlas ◽  
Poor Outcomes

The small leucine-rich proteoglycan (SLRP) family is widely expressed in extracellular matrix and aggravates tumor progression. However, epiphycan (EPYC), as a member of the SLRPs family, its biological function in cancer has not been confirmed. Thus, we aimed to clarify the role of EPYC in progression of ovarian cancer (OC), and further analyze the molecular mechanisms implicated in tumorigenesis. Here, we analyzed the differential expression genes of GSE38734, including 4 matched primary OC and metastatic tissues. We obtained OC RNAseqs data from the Cancer Genome Atlas (TCGA) and analyzed the correlation between EPYC expression and OC staging, pathological grading, etc. The expression of EPYC in OC and normal ovarian tissues was compared in Oncomine website. We used siRNAs to interfere the expression of EPYC in ovarian cancer cell line SKOV3. Scratch test, transwell-matrigel chamber, CCK8 assay were used to detect the changes of SKOV3 migration, invasion and proliferation ability after EPYC was interfered. We used R software to make GO and KEGG analysis of related genes of EPYC. We used the Hitpredict website to predict interacting proteins. The results showed that the expression of EPYC in metastatic ovarian cancer was higher than primary ovarian cancer, and that in primary cancer was higher than normal ovaries. After siRNA interferes with EPYC expression, the migration, invasion and proliferation of SKOV3 cells were weakened. EPYC mainly played a role in ECM organization, and involved in PI3K/Akt, focal adhesion signaling pathways. EPYC might interact with PLCG2 and CRK, and be involved in signal transduction.

scholarly journals A Novel Automatic Platform Based on Nanostructured Microfluidic Chip for Isolating and Identification of Circulating Tumor Cells

2021 ◽  
Author(s):  
Hei-Jen Jou ◽  
Li-Yun Chou ◽  
Wen-Chun Chang ◽  
Hsin-Cheng Ho ◽  
Wan-Ting Zhang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Microfluidic Chip ◽  
Detection System ◽  
Ovarian Cancer Cell Line ◽  
Capture Rate ◽  
Cancer Cell Line ◽  
Circulating Tumor Cell ◽  
Test Range ◽  
Cell Counts ◽  
Skov3 Cells

Abstract Circulating tumor cell (CTC) is commonly used as biomarker for early detection, prognostication, decision making, and evaluation of the therapeutic efficacy in cancer treatment. Unfortunately, the poor reproducibility and limited sensitivity with the CTC detection have limited its potential impact on clinical management. A reliable automated CTC detection system is therefore needed. We have designed an automated microfluidic chip-based CTC detection system consisting of three main parts: V-BioChip, Cell RevealTM enrichment and staining system, and an automatic scanning and locating system. We hypothesized this novel system can reliably detect CTC from clinical specimens. SKOV3 ovarian cancer cell line was used first to test the reliability of our system. Ten healthy volunteers, 5 patients with benign ovarian tumors, and 8 patients with epithelial ovarian cancer (EOC) were recruited after obtaining written consents to validate the CTC capturing efficacy in the peripheral blood. The capture rates for spiking test in SKOV3 cells were as 48.3% and 89.6% using EpCAM antibody alone and a combined EpCAM antibody and N-cadherin antibody, respectively. The system was sensitive to detection of low cell count and showed a linear relationship with the cell counts in our test range. The sensitivity and specificity were 62.5% and 100% when CTC was used as a biomarker for EOC. Our results demonstrated that this automatic CTC platform has a high capture rate and is feasible for detection of CTCs in EOC.

scholarly journals Bromodomain-containing protein 4 regulates interleukin-34 expression in mouse ovarian cancer cells

2020 ◽  
Vol 40 (1) ◽  
Author(s):  
Nanumi Han ◽  
Delnur Anwar ◽  
Naoki Hama ◽  
Takuto Kobayashi ◽  
Hidefumi Suzuki ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Tumor Growth ◽  
Tumor Progression ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Ovarian Cancer Cell Line ◽  
Cancer Cell Line ◽  
Ovarian Cancer Cells ◽  
Mouse Tumor

Abstract Background Interleukin (IL)-34 acts as an alternative ligand for the colony-stimulating factor-1 receptor and controls the biology of myeloid cells, including survival, proliferation, and differentiation. IL-34 has been reported to be expressed in cancer cells and to promote tumor progression and metastasis of certain cancers via the promotion of angiogenesis and immunosuppressive macrophage differentiation. We have shown in our previous reports that targeting IL-34 in chemo-resistant tumors in vitro resulted in a remarkable inhibition of tumor growth. Also, we reported poor prognosis in patients with IL-34-expressing tumor. Therefore, blocking of IL-34 is considered as a promising therapeutic strategy to suppress tumor progression. However, the molecular mechanisms that control IL-34 production are still largely unknown. Methods IL-34 producing ovarian cancer cell line HM-1 was treated by bromodomain and extra terminal inhibitor JQ1. The mRNA and protein expression of IL-34 was evaluated after JQ1 treatment. Chromatin immunoprecipitation was performed to confirm the involvement of bromodomain-containing protein 4 (Brd4) in the regulation of the Il34 gene. Anti-tumor effect of JQ1 was evaluated in mouse tumor model. Results We identified Brd4 as one of the critical molecules that regulate Il34 expression in cancer cells. Consistent with this, we found that JQ1 is capable of efficiently suppressing the recruitment of Brd4 to the promotor region of Il34 gene. Additionally, JQ1 treatment of mice bearing IL-34-producing tumor inhibited the tumor growth along with decreasing Il34 expression in the tumor. Conclusion The results unveiled for the first time the responsible molecule Brd4 that regulates Il34 expression in cancer cells and suggested its possibility as a treatment target.

scholarly journals 3-Hydroxypropane-1,2-Diyl Dipalmitoleate—A Natural Compound with Dual Roles (CB1 Agonist/FAAH1 Blocker) in Inhibiting Ovarian Cancer Cell Line

2021 ◽  
Vol 14 (3) ◽  
pp. 255
Author(s):  
Christina Vijayaraghavan Sathynathan ◽  
Lakshmi Sundaram Raman ◽  
Sivamurugan Vajiravelu ◽  
Thirumal D. Kumar ◽  
Thyagarajan Sadras Panchatcharam ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Line ◽  
Cancer Cell ◽  
Natural Compound ◽  
Molecular Mechanisms ◽  
Ovarian Cancer Cell ◽  
Ovarian Cancer Cell Line ◽  
Acid Amide ◽  
Cancer Cell Line ◽  
Dual Roles

Though it was once known that upregulated Cannabinoid Receptor (CB1) and downregulated Fatty Acid Amide Hydrolase (FAAH1) are associated with tumour aggressiveness and metastasis, it is now clear that upregulated CB1 levels more than a certain point cause accumulation of ceramide and directs cells to apoptosis. Hence, CB1 analogues/FAAH1 blockers are explored widely as anticancer drugs. There are reports on CB1-agonists and FAAH1-blockers separately, however, dual activities along with ovarian cancer-specific links are not established for any natural compound. With this setting, we describe for the first time the isolation of 3-hydroxypropane-1,2-diyl dipalmitoleate (564.48 Da) from a marine snail, Conus inscriptus, which binds to both CB1 and FAAH1 (glide energies: −70.61 and −30.52 kcal/mol, respectively). MD simulations indicate stable compound–target interaction for a minimum of 50 nanoseconds with relative invariabilities in Rg. The compound inhibited ovarian cancer cell line, PA1 at 1.7 μM. Structural and chemical interpretation of the compound (C2) was done using FT-IR, GC-MS, ESI-MS, 1H and 13C-NMR (1 and 2D). Furthermore, a probable route for gram-scale synthesis of C2 is hinted herein. With the available preliminary data, molecular mechanisms involving dual roles for this potent molecule must be elucidated to understand the possibilities of usage as an anticancer drug.

The Anti-Proliferative Effect of Flavonoid Nanoparticles on the Human Ovarian Cancer Cell Line SK0V3

2020 ◽  
Vol 20 (10) ◽  
pp. 6040-6046
Author(s):  
Chunyan Zhang ◽  
Xueqing Li ◽  
Shuangling Jin ◽  
Huizhen Zhang ◽  
Rui Wang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Treatment Group ◽  
Cell Line ◽  
Tumor Cells ◽  
Ovarian Cancer Cell ◽  
Ovarian Cancer Cell Line ◽  
Cancer Cell Line ◽  
Control Group ◽  
Human Ovarian Cancer ◽  
Skov3 Cells

To investigate the anti-proliferative effect of flavonoid nanoparticles on the human ovarian cancer cell line SKOV3. Ten nude mice were intraperitoneally inoculated with the human ovarian cancer SKOV3 cell mixture. The treatment group received tail vein injections with 1.25 mg/kg of flavonol, once every 3 days, 0.2 mL each time, for a total of 12 times. The control group was a tumor model that was injected with 50 mL/L glucose solution; it was observed in Lacquerin Group as the Laccase Nanoparticle Group. Tumor quality was recorded after treatment. The morphology of tumor cells in the two groups was observed by fluorescence microscopy. MTS was used to measure the value of tumor cells in the two groups after administration. Apoptosis of SKOV3 cells was detected by flow cytometry using a tumor cell suspension. The MTT results showed a decreased growth rate of SKOV3 cells with an increase in the mass concentration of flavonoid nanoparticles. The nude mice in the control group had scattered cauliflower-like tumor nodules. The treatment group only showed very small granular tumor nodules. The tumor mass within the treatment group was comparable (P > 0.05), but was lower than that in the control group (P < 0.05). The morphology of the tumor cells in the treatment group became longer and thinner and showed a slender spindle shape. Some high-temperature treated cells even appeared star-shaped, and the cell bodies were significantly broadened. Flow cytometry results showed significantly increased apoptosis of the SKOV3 cells after treatment with flavonoid nanoparticles. The MTS results showed a significantly slowed proliferation rate of SKOV3 cells after two days of administering flavonoid nanoparticles (P < 0.05). Flavonoid nanoparticles were nontoxic, and decreased cell proliferation of and promoted apoptosis in an ovarian cancer cell line.

scholarly journals CD105 Is Expressed in Ovarian Cancer Precursor Lesions and Is Required for Metastasis to the Ovary

Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1710 ◽  
Author(s):  
Bai ◽  
Zhu ◽  
Coffman ◽  
Vlad ◽  
Schwartz ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Animal Models ◽  
Fallopian Tube ◽  
Critical Role ◽  
Cancer Cell Line ◽  
The Cancer Genome Atlas ◽  
Abdominal Tumor ◽  
Cancer Spread ◽  
Cancer Genome Atlas ◽  
Using Data

: Most high‐grade serous ovarian cancers (HGSCs) initiate from the fallopian tube epithelium and then metastasize to the ovary and throughout the abdomen. Genomic analyses suggest that most HGSCs seed the ovary prior to abdominal dissemination. Similarly, animal models support a critical role for the ovary in driving abdominal dissemination. Thus, HGSC cell recruitment to the ovary appears to be a critical component of HGSC cell metastasis. We sought to identify factors driving HGSC recruitment to the ovary. We identified CD105 (endoglin, or ENG, a TGF‐ receptor family member) as a mediator of HGSC cell ovarian recruitment. We found that CD105 was expressed on both serous tubal intraepithelial carcinoma (STIC) cells (STICs‐HGSC precursors in the fallopian tube epithelium) and HGSC cells. Using data from The Cancer Genome Atlas (TCGA) and the Cancer Cell Line Encyclopedia (CCLE), we showed that high CD105 expression by HGSC cells correlated with a metastatic signature. Furthermore, intravenous injection of CD105(+) HGSC tumor cells, but not CD105(−), resulted in ovarian-specific metastasis and abdominal dissemination of disease. CD105 knockdown or blockade with a clinically relevant CD105-neutralizing mAb (TRC105), inhibited HGSC metastasis, reduced ascites, and impeded growth of abdominal tumor nodules, thereby improving overall survival in animal models of ovarian cancer. CD105 knockdown was associated with a reduction in TGF-signaling. Together, our data support CD105 as a critical mediator of ovarian cancer spread to the ovary and implicate it as a potential therapeutic target.

scholarly journals RASSF1A and the Taxol Response in Ovarian Cancer

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Susannah Kassler ◽  
Howard Donninger ◽  
Michael J. Birrer ◽  
Geoffrey J. Clark
Keyword(s):  
Ovarian Cancer ◽  
Ovarian Cancer Cell ◽  
Ovarian Cancer Cell Line ◽  
Cancer Cell Line ◽  
Suppressor Gene ◽  
Epigenetic Therapy ◽  
Methyl Transferase ◽  
Primary Ovarian Cancer ◽  
Taxol Resistance ◽  
Ovarian Tumor Cells

The RASSF1A tumor suppressor gene is frequently inactivated by promoter methylation in human tumors. The RASSF1A protein forms an endogenous complex with tubulin and promotes the stabilization of microtubules. Loss of RASSF1A expression sensitizes cells to microtubule destabilizing stimuli. We have observed a strong correlation between the loss of RASSF1A expression and the development of Taxol resistance in primary ovarian cancer samples. Thus, we sought to determine if RASSF1A levels could dictate the response to Taxol and whether an epigenetic therapy approach might be able to reverse the Taxol resistant phenotype of RASSF1A negative ovarian tumor cells. We found that knocking down RASSF1A expression in an ovarian cancer cell line inhibited Taxol-mediated apoptosis and promoted cell survival during Taxol treatment. Moreover, using a combination of small molecule inhibitors of DNA Methyl Transferase enzymes, we were able restore RASSF1A expression and Taxol sensitivity. This identifies a role for RASSF1A in modulating the tumor response to Taxol and provides proof of principal for the use of epigenetic therapy to overcome Taxol resistance.

scholarly journals An Automatic Platform Based on Nanostructured Microfluidic Chip for Isolating and Identification of Circulating Tumor Cells

Micromachines ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 473
Author(s):  
Hei-Jen Jou ◽  
Li-Yun Chou ◽  
Wen-Chun Chang ◽  
Hsin-Cheng Ho ◽  
Wan-Ting Zhang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Microfluidic Chip ◽  
Detection System ◽  
Ovarian Cancer Cell Line ◽  
Capture Rate ◽  
Cancer Cell Line ◽  
Circulating Tumor Cell ◽  
Test Range ◽  
Cell Counts ◽  
Skov3 Cells

Circulating tumor cell (CTC) test is currently used as a biomarker in cancer treatment. Unfortunately, the poor reproducibility and limited sensitivity with the CTC detection have limited its potential impact on clinical application. A reliable automated CTC detection system is therefore needed. We have designed an automated microfluidic chip-based CTC detection system and hypothesize this novel system can reliably detect CTC from clinical specimens. SKOV3 ovarian cancer cell line was used first to test the reliability of our system. Ten healthy volunteers, 5 patients with benign ovarian tumors, and 8 patients with epithelial ovarian cancer (EOC) were recruited to validate the CTC capturing efficacy in the peripheral blood. The capture rates for spiking test in SKOV3 cells were 48.3% and 89.6% by using anti-EpCAM antibody alone and a combination of anti-EpCAM antibody and anti-N-cadherin antibody, respectively. The system was sensitive to detection of low cell count and showed a linear relationship with the cell counts in our test range. The sensitivity and specificity were 62.5% and 100% when CTC was used as a biomarker for EOC. Our results demonstrated that this automatic CTC platform has a high capture rate and is feasible for detection of CTCs in EOC.

scholarly journals HNRNPH1-stabilized LINC00662 promotes ovarian cancer progression by activating the GRP78/p38 pathway

Oncogene ◽  
2021 ◽  
Author(s):  
Yong Wu ◽  
Qinhao Guo ◽  
Xingzhu Ju ◽  
Zhixiang Hu ◽  
Lingfang Xia ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Progression ◽  
Prognostic Indicator ◽  
Mapk Signaling ◽  
The Cancer Genome Atlas ◽  
Cancer Genome Atlas ◽  
Proliferation And Metastasis ◽  
Nuclear Ribonucleoprotein

AbstractNumerous studies suggest an important role for copy number alterations (CNAs) in cancer progression. However, CNAs of long intergenic noncoding RNAs (lincRNAs) in ovarian cancer (OC) and their potential functions have not been fully investigated. Here, based on analysis of The Cancer Genome Atlas (TCGA) database, we identified in this study an oncogenic lincRNA termed LINC00662 that exhibited a significant correlation between its CNA and its increased expression. LINC00662 overexpression is highly associated with malignant features in OC patients and is a prognostic indicator. LINC00662 significantly promotes OC cell proliferation and metastasis in vitro and in vivo. Mechanistically, LINC00662 is stabilized by heterogeneous nuclear ribonucleoprotein H1 (HNRNPH1). Moreover, LINC00662 exerts oncogenic effects by interacting with glucose-regulated protein 78 (GRP78) and preventing its ubiquitination in OC cells, leading to activation of the oncogenic p38 MAPK signaling pathway. Taken together, our results define an oncogenic role for LINC00662 in OC progression mediated via GRP78/p38 signaling, with potential implications regarding therapeutic targets for OC.

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