Quantitative Biophysical Metrics for Rapid Evaluation of Ovarian Cancer Metastatic Potential

2022 ◽  
Author(s):  
Apratim Mukherjee ◽  
Haonan Zhang ◽  
Katherine Ladner ◽  
Megan Brown ◽  
Jacob Urbanski ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Mouse Model ◽  
Cancer Progression ◽  
Metastatic Potential ◽  
Actin Stress Fiber ◽  
Fiber Network ◽  
Progression Model ◽  
Ovarian Cancer Cell Lines ◽  
Fiber Spacing ◽  
Cellular Markers

Ovarian cancer is routinely diagnosed long after the disease has metastasized through the fibrous sub-mesothelium. Despite extensive research in the field linking ovarian cancer progression to increasingly poor prognosis, there are currently no validated cellular markers or hallmarks of ovarian cancer that can predict metastatic potential. To discern disease progression across a syngeneic mouse ovarian cancer progression model, here, we fabricated extracellular-matrix mimicking suspended fiber networks: crosshatches of mismatch diameters for studying protrusion dynamics, aligned same diameter networks of varying inter-fiber spacing for studying migration, and aligned nanonets for measuring cell forces. We found that migration correlated with disease, while force-disease biphasic relationship exhibited f-actin stress-fiber network dependence. However, unique to suspended fibers, coiling occurring at tips of protrusions and not the length or breadth of protrusions displayed strongest correlation with metastatic potential. To confirm that our findings were more broadly applicable beyond the mouse model, we repeated our studies in human ovarian cancer cell lines and found that the biophysical trends were consistent with our mouse model results. Altogether, we report complementary high throughput and high content biophysical metrics capable of identifying ovarian cancer metastatic potential on time scale of hours. [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text]

scholarly journals Changes in Gene Expression and Cellular Architecture in an Ovarian Cancer Progression Model

PLoS ONE ◽  
2011 ◽  
Vol 6 (3) ◽  
pp. e17676 ◽  
Author(s):  
Amy L. Creekmore ◽  
William T. Silkworth ◽  
Daniela Cimini ◽  
Roderick V. Jensen ◽  
Paul C. Roberts ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ovarian Cancer ◽  
Cancer Progression ◽  
Cellular Architecture ◽  
Progression Model

scholarly journals Paclitaxel-Induced Src Activation Is Inhibited by Dasatinib Treatment, Independently of Cancer Stem Cell Properties, in a Mouse Model of Ovarian Cancer

Cancers ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 243 ◽  
Author(s):  
Elif Kadife ◽  
Emily Chan ◽  
Rodney Luwor ◽  
George Kannourakis ◽  
Jock Findlay ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Progression ◽  
Mononuclear Cells ◽  
Ovarian Cancer Cells ◽  
Small Subset ◽  
Ovarian Carcinomas ◽  
Ovarian Cancer Cell Lines ◽  
Benign Ovarian Tumours ◽  
Src Activation

Approximately seventy percent of ovarian cancer patients succumb to the disease within the first 5 years of diagnosis, even after successful surgery and effective chemotherapy treatment. A small subset of chemotherapy resistant cancer stem cells (CSCs) cause relapse of ovarian cancers. This study investigated the association between paclitaxel-mediated Src activation (p-Src) and CSC populations in driving ovarian cancer progression. We demonstrate that patients with high-stage serous ovarian carcinomas have significantly elevated levels of p-Src, compared to patient with low-stage and benign ovarian tumours. Additionally, p-Src was significantly enhanced in ascites-derived tumour cells obtained from recurrent patients, compared to chemonaïve patients. Paclitaxel treatment increased Src activation in ovarian cancer cells, causing enrichment of CSC marker expression in the surviving cells in vitro and in xenografts of nude mice. Dasatinib in combination with paclitaxel significantly suppressed p-Src in ovarian cancer cell lines and xenografts but had no effect on the expression of CSC markers. However, combination of paclitaxel and Dasatinib showed lower trend in invasion in liver and pancreas, compared to paclitaxel-only treatment. The tumours treated with combination therapy also had significantly lower infiltration of mononuclear cells. Robust recurrent tumour growth was observed in all mice groups after termination of treatments. The above results suggest that Dasatinib-mediated inhibition of p-Src may not be crucial for paclitaxel-induced CSC-mediated recurrence in ovarian cancer.

scholarly journals The microRNA-205-5p is correlated to metastatic potential of 21T series: A breast cancer progression model

PLoS ONE ◽  
2017 ◽  
Vol 12 (3) ◽  
pp. e0173756 ◽  
Author(s):  
L. Stankevicins ◽  
A. Barat ◽  
P. Dessen ◽  
Y. Vassetzky ◽  
C. V. de Moura Gallo
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Metastatic Potential ◽  
Breast Cancer Progression ◽  
Progression Model

scholarly journals Targeting Ovarian Cancer Cells Overexpressing CD44 with Immunoliposomes Encapsulating Glycosylated Paclitaxel

2019 ◽  
Vol 20 (5) ◽  
pp. 1042 ◽  
Author(s):  
Apriliana Cahya Khayrani ◽  
Hafizah Mahmud ◽  
Aung Ko Ko Oo ◽  
Maram H. Zahra ◽  
Miharu Oze ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Stem Cell Marker ◽  
Ovarian Cancer Cells ◽  
Cancer Therapies ◽  
Ovarian Cancer Cell Lines ◽  
Tumor Selective

Paclitaxel (PTX) is one of the front-line drugs approved for the treatment of ovarian cancer. However, the application of PTX is limited due to the significant hydrophobicity and poor pharmacokinetics. We previously reported target-directed liposomes carrying tumor-selective conjugated antibody and encapsulated glycosylated PTX (gPTX-L) which successfully overcome the PTX limitation. The tubulin stabilizing activity of gPTX was equivalent to that of PTX while the cytotoxic activity of gPTX was reduced. In human ovarian cancer cell lines, SK-OV-3 and OVK18, the concentration at which cell growth was inhibited by 50% (IC50) for gPTX range from 15–20 nM, which was sensitive enough to address gPTX-L with tumor-selective antibody coupling for ovarian cancer therapy. The cell membrane receptor CD44 is associated with cancer progression and has been recognized as a cancer stem cell marker including ovarian cancer, becoming a suitable candidate to be targeted by gPTX-L therapy. In this study, gPTX-loading liposomes conjugated with anti-CD44 antibody (gPTX-IL) were assessed for the efficacy of targeting CD44-positive ovarian cancer cells. We successfully encapsulated gPTX into liposomes with the loading efficiency (LE) more than 80% in both of gPTX-L and gPTX-IL with a diameter of approximately 100 nm with efficacy of enhanced cytotoxicity in vitro and of convenient treatment in vivo. As the result, gPTX-IL efficiently suppressed tumor growth in vivo. Therefore gPTX-IL could be a promising formulation for effective ovarian cancer therapies.

scholarly journals Prognostic values of GMPS, PR, CD40, and p21 in ovarian cancer

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e6301 ◽  
Author(s):  
Ping Wang ◽  
Zengli Zhang ◽  
Yujie Ma ◽  
Jun Lu ◽  
Hu Zhao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ovarian Cancer ◽  
Cancer Patients ◽  
Differential Expression ◽  
Cancer Progression ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Progression Model ◽  
Cancer Genome Atlas ◽  
Genome Atlas

Early detection and prediction of prognosis and treatment responses are all the keys in improving survival of ovarian cancer patients. This study profiled an ovarian cancer progression model to identify prognostic biomarkers for ovarian cancer patients. Mouse ovarian surface epithelial cells (MOSECs) can undergo spontaneous malignant transformation in vitro cell culture. These were used as a model of ovarian cancer progression for alterations in gene expression and signaling detected using the Illumina HiSeq2000 Next-Generation Sequencing platform and bioinformatical analyses. The differential expression of four selected genes was identified using the gene expression profiling interaction analysis (http://gepia.cancer-pku.cn/) and then associated with survival in ovarian cancer patients using the Cancer Genome Atlas dataset and the online Kaplan–Meier Plotter (http://www.kmplot.com) data. The data showed 263 aberrantly expressed genes, including 182 up-regulated and 81 down-regulated genes between the early and late stages of tumor progression in MOSECs. The bioinformatic data revealed four genes (i.e., guanosine 5′-monophosphate synthase (GMPS), progesterone receptor (PR), CD40, and p21 (cyclin-dependent kinase inhibitor 1A)) to play an important role in ovarian cancer progression. Furthermore, the Cancer Genome Atlas dataset validated the differential expression of these four genes, which were associated with prognosis in ovarian cancer patients. In conclusion, this study profiled differentially expressed genes using the ovarian cancer progression model and identified four (i.e., GMPS, PR, CD40, and p21) as prognostic markers for ovarian cancer patients. Future studies of prospective patients could further verify the clinical usefulness of this four-gene signature.

scholarly journals The Potential Role of iNOS in Ovarian Cancer Progression and Chemoresistance

2019 ◽  
Vol 20 (7) ◽  
pp. 1751 ◽  
Author(s):  
Kielbik ◽  
Szulc-Kielbik ◽  
Klink
Keyword(s):  
Nitric Oxide ◽  
Ovarian Cancer ◽  
Cancer Progression ◽  
Inos Expression ◽  
No Production ◽  
Patient Death ◽  
Ovarian Cancer Cell Lines ◽  
Risk Of Disease ◽  
High Level

Inducible nitric oxide synthase (iNOS), the enzyme responsible for nitric oxide (NO) production, is not present in most cells under normal conditions. The expression of its mRNA, as well as its protein synthesis and full enzymatic activity, undergoes multilevel regulation including transcriptional and posttranscriptional mechanisms, the availability of iNOS substrate and cofactors and oxygen tension. However, in various malignant diseases, such as ovarian cancer, the intracellular mechanisms controlling iNOS are dysregulated, resulting in the permanent induction of iNOS expression and activation. The present review summarizes the multistaged processes occurring in normal cells that promote NO synthesis and focuses on factors regulating iNOS expression in ovarian cancer. The possible involvement of iNOS in the chemoresistance of ovarian cancer and its potential as a prognostic/predictive factor in the course of disease development are also reviewed. According to the available yet limited data, it is difficult to draw unequivocal conclusions on the pros and cons of iNOS in ovarian cancer. Most clinical data support the hypothesis that high levels of iNOS expression in ovarian tumors are associated with a greater risk of disease relapse and patient death. However, in vitro studies with various ovarian cancer cell lines indicate a correlation between a high level of iNOS expression and sensitivity to cisplatin.

scholarly journals Sphingolipid metabolites modulate dielectric characteristics of cells in a mouse ovarian cancer progression model

2013 ◽  
Vol 5 (6) ◽  
pp. 843-852 ◽  
Author(s):  
Alireza Salmanzadeh ◽  
Elizabeth S. Elvington ◽  
Paul C. Roberts ◽  
Eva M. Schmelz ◽  
Rafael V. Davalos
Keyword(s):  
Ovarian Cancer ◽  
Cancer Progression ◽  
Dielectric Characteristics ◽  
Progression Model
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