An ovarian spheroid based tumor model that represents vascularized tumors and enables the investigation of nanomedicine therapeutics

Singh, Manu Smriti; Goldsmith, Meir; Thakur, Kavita; Chatterjee, Sushmita; Landesman-Milo, Dalit; Levy, Tally; Kunz-Schughart, Leoni A.; Barenholz, Yechezkel; Peer, Dan

doi:10.1039/c9nr09572a

Cited by 22 publications

(15 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The use of round-bottomed, ULA plates have assisted in the identification of Nectin-4 as essential for adhesion events in early spheroid formation of HGSOC cell lines, and as potential targets to improve chemotherapeutic sensitivity ( Boylan et al, 2020 ). Pre-formed OVCAR-8 spheroids grown in round-bottomed ULA plates and further embedded as single spheroids in Matrigel, developed vascularization after subcutaneous transplantation into athymic nude mice, enabling the evaluation of therapeutics such as the anti-angiogenic bevacizumab and the nano-drug Doxil ® ( Singh et al, 2020 ).…”

Section: 3d In Vitro Ovarian Cancer Modelsmentioning

confidence: 99%

Three-Dimensional Modelling of Ovarian Cancer: From Cell Lines to Organoids for Discovery and Personalized Medicine

Yee

Dickson

Muntasir

et al. 2022

Front. Bioeng. Biotechnol.

View full text Add to dashboard Cite

Ovarian cancer has the highest mortality of all of the gynecological malignancies. There are several distinct histotypes of this malignancy characterized by specific molecular events and clinical behavior. These histotypes have differing responses to platinum-based drugs that have been the mainstay of therapy for ovarian cancer for decades. For histotypes that initially respond to a chemotherapeutic regime of carboplatin and paclitaxel such as high-grade serous ovarian cancer, the development of chemoresistance is common and underpins incurable disease. Recent discoveries have led to the clinical use of PARP (poly ADP ribose polymerase) inhibitors for ovarian cancers defective in homologous recombination repair, as well as the anti-angiogenic bevacizumab. While predictive molecular testing involving identification of a genomic scar and/or the presence of germline or somatic BRCA1 or BRCA2 mutation are in clinical use to inform the likely success of a PARP inhibitor, no similar tests are available to identify women likely to respond to bevacizumab. Functional tests to predict patient response to any drug are, in fact, essentially absent from clinical care. New drugs are needed to treat ovarian cancer. In this review, we discuss applications to address the currently unmet need of developing physiologically relevant in vitro and ex vivo models of ovarian cancer for fundamental discovery science, and personalized medicine approaches. Traditional two-dimensional (2D) in vitro cell culture of ovarian cancer lacks critical cell-to-cell interactions afforded by culture in three-dimensions. Additionally, modelling interactions with the tumor microenvironment, including the surface of organs in the peritoneal cavity that support metastatic growth of ovarian cancer, will improve the power of these models. Being able to reliably grow primary tumoroid cultures of ovarian cancer will improve the ability to recapitulate tumor heterogeneity. Three-dimensional (3D) modelling systems, from cell lines to organoid or tumoroid cultures, represent enhanced starting points from which improved translational outcomes for women with ovarian cancer will emerge.

show abstract

Section: 3d In Vitro Ovarian Cancer Modelsmentioning

confidence: 99%

Three-Dimensional Modelling of Ovarian Cancer: From Cell Lines to Organoids for Discovery and Personalized Medicine

Yee

Dickson

Muntasir

et al. 2022

Front. Bioeng. Biotechnol.

View full text Add to dashboard Cite

show abstract

“…Since it has been observed in vivo that ovarian cancers often tend to grow in ascites as cell clusters (spheroids) having the potential to metastasize [ 29 , 30 , 31 ], the spheroid model could be particularly relevant to study, in vitro, the ovarian cancer biology and how EVs contribute to cancer progression, taking advantage of an approach that is more consistent with in vivo situation. Indeed, several studies on ovarian cancer have already suggested that the culture model choice can impact, for example, sensitivity to chemotherapeutic agents [ 24 , 32 ].…”

Section: Introductionmentioning

confidence: 99%

Cancer Three-Dimensional Spheroids Mimic In Vivo Tumor Features, Displaying “Inner” Extracellular Vesicles and Vasculogenic Mimicry

Giusti

Poppa

D’Ascenzo

et al. 2022

IJMS

View full text Add to dashboard Cite

The role of extracellular vesicles (EVs) as mediators of cell-to-cell communication in cancer progression is widely recognized. In vitro studies are routinely performed on 2D culture models, but recent studies suggest that 3D cultures could represent a more valid model. Human ovarian cancer cells CABA I were cultured by the hanging drop method to form tumor spheroids, that were moved to low adhesion supports to observe their morphology by Scanning Electron Microscopy (SEM) and to isolate the EVs. EVs release was verified by SEM and their identity confirmed by morphology (Transmission Electron Microscopy, TEM), size distribution (Nanoparticles Tracking Analysis), and markers (CD63, CD9, TSG-101, Calnexin). CABA I form spheroids with a clinically relevant size, above 400 μm; they release EVs on their external surface and also trap “inner” EVs. They also produce vasculogenic mimicry-like tubules, that bulge from the spheroid and are composed of a hollow lumen delimited by tumor cells. CABA I can be grown as multicellular spheroids to easily isolate EVs. The presence of features typical of in vivo tumors (inner entrapped EVs and vasculogenic mimicry) suggests their use as faithful experimental models to screen therapeutic drugs targeting these pro-tumorigenic processes.

show abstract

“…As the most common gynaecological malignant tumour in the clinic, ovarian cancer ranks first in terms of mortality rate among various gynaecological tumours (9). As to its treatment, surgical treatment combined with postoperative adjuvant chemoradiotherapy and biological therapy is the main approach.…”

Section: Discussionmentioning

confidence: 99%

Effects of adiponectin, plasma D-dimer, inflammation and tumor markers on clinical characteristics and prognosis of patients with ovarian cancer

Li¹,

Sun²,

Chen³

et al. 2022

J Med Biochemistry

View full text Add to dashboard Cite

[Abstract] Objective: To investigate the effects of adiponectin (ADPN), plasma D-dimer (D-D), inflammation and tumor markers on clinical characteristics and prognosis of patients with ovarian cancer. Methods: A total of 80 patients with ovarian cancer treated in our hospital from April 2017 to November 2019 were enrolled as study subjects and evenly divided into observation group (patients with ovarian cancer) and control group (patients with benign ovarian tumor) based on the results of postoperative pathological biopsy. The levels of ADPN, plasma D-D, inflammatory factors and serum tumor markers [carbohydrate antigen 125 (CA125), human epididymis protein 4 (HE4) and risk of ovarian malignancy algorithm (ROMA)] were compared between the two groups. The diagnostic value of serum tumor markers CA125, HE4 and ROMA in ovarian cancer was explored. The correlations of the changes of ROMA with the changes in the levels of ADPN, plasma D-D, high-sensitivity C-reactive protein (hs-CRP), CA125 and HE4 were analyzed. Additionally, the related risk factors affecting the development of ovarian cancer were subjected to univariate and multivariate logistic regression analyses. Results: In comparison with control group, observation group exhibited a lowered ADPN level (p<0.05), notably raised levels of plasma D-D, inflammatory factors hs-CRP and interleukin-6 (IL-6) and serum tumor markers CA125 and HE4 and an evidently increased ROMA (p<0.05). Besides, the detection of serum ROMA showed the highest specificity and sensitivity and low false positive rate and false negative rate. The changes of ROMA were positively correlated with the changes in the levels of plasma D-D, hs-CRP, CA125 and HE4 (p<0.05), and negatively associated with the changes in ADPN level (p<0.05). The results of univariate analysis showed that abnormal ADPN, D-D, hs-CRP, IL-6, CA125 and HE4 levels were related risk factors affecting the development of ovarian cancer. It was found through multivariate logistic regression analysis that decreased ADPN level and increased D-D, hs-CRP, IL-6, CA125 and HE4 levels were independent risk factors affecting the development of ovarian cancer. Conclusion: In the case of ovarian cancer, the ADPN level declines, while the levels of plasma D-D, inflammatory factors, and serum tumor markers CA125, HE4 and ROMA rise obviously. Besides, the ROMA level displays a positive relation to the content of CA125, HE4, plasma D-D and inflammatory factors and a negative association with ADPN level.

show abstract

An ovarian spheroid based tumor model that represents vascularized tumors and enables the investigation of nanomedicine therapeutics

Abstract: 3D tumors created by simple subcutaneous spheroid injection represents a robust and more vascular murine tumor model and can be a relevant platform to test anti-cancer therapy.

Cited by 22 publications

References 37 publications

Three-Dimensional Modelling of Ovarian Cancer: From Cell Lines to Organoids for Discovery and Personalized Medicine

Three-Dimensional Modelling of Ovarian Cancer: From Cell Lines to Organoids for Discovery and Personalized Medicine

Cancer Three-Dimensional Spheroids Mimic In Vivo Tumor Features, Displaying “Inner” Extracellular Vesicles and Vasculogenic Mimicry

Effects of adiponectin, plasma D-dimer, inflammation and tumor markers on clinical characteristics and prognosis of patients with ovarian cancer

Contact Info

Product

Resources

About