Comparative Analysis of Cell–Cell Contact Abundance in Ovarian Carcinoma Cells Cultured in Two- and Three-Dimensional In Vitro Models

Tumor resistance to therapy is associated with the 3D organization and peculiarities of the tumor microenvironment, of which intercellular adhesion is a key participant. In this work, the abundance of contact proteins was compared in SKOV-3 and SKOV-3.ip human ovarian adenocarcinoma cell lines, cult...

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Main Authors: Olga M. Kutova, Ludmila M. Sencha, Anton D. Pospelov, Olga E. Dobrynina, Anna A. Brilkina, Elena I. Cherkasova, Irina V. Balalaeva
Format: Article
Language:English
Published: MDPI AG 2020-12-01
Series:Biology
Subjects:
Online Access:https://www.mdpi.com/2079-7737/9/12/446
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author Olga M. Kutova
Ludmila M. Sencha
Anton D. Pospelov
Olga E. Dobrynina
Anna A. Brilkina
Elena I. Cherkasova
Irina V. Balalaeva
author_facet Olga M. Kutova
Ludmila M. Sencha
Anton D. Pospelov
Olga E. Dobrynina
Anna A. Brilkina
Elena I. Cherkasova
Irina V. Balalaeva
author_sort Olga M. Kutova
collection DOAJ
description Tumor resistance to therapy is associated with the 3D organization and peculiarities of the tumor microenvironment, of which intercellular adhesion is a key participant. In this work, the abundance of contact proteins was compared in SKOV-3 and SKOV-3.ip human ovarian adenocarcinoma cell lines, cultivated in monolayers, tumor spheroids and collagen hydrogels. Three-dimensional models were characterized by extremely low expression of basic molecules of adherens junctions E-cadherin and demonstrated a simultaneous decrease in desmosomal protein desmoglein-2, gap junction protein connexin-43 and tight junction proteins occludin and ZO-1. The reduction in the level of contact proteins was most pronounced in collagen hydrogel, accompanied by significantly increased resistance to treatment with doxorubicin and targeted anticancer toxin DARPin-LoPE. Thus, we suggest that 3D models of ovarian cancer, especially matrix-based models, tend to recapitulate tumor microenvironment and treatment responsiveness to a greater extent than monolayer culture, so they can be used as a highly relevant platform for drug efficiency evaluation.
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spelling doaj.art-820487cace494cfc9ba6bf4d3c7ce23b2023-11-20T23:34:23ZengMDPI AGBiology2079-77372020-12-0191244610.3390/biology9120446Comparative Analysis of Cell–Cell Contact Abundance in Ovarian Carcinoma Cells Cultured in Two- and Three-Dimensional In Vitro ModelsOlga M. Kutova0Ludmila M. Sencha1Anton D. Pospelov2Olga E. Dobrynina3Anna A. Brilkina4Elena I. Cherkasova5Irina V. Balalaeva6The Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Ave., 603950 Nizhny Novgorod, RussiaThe Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Ave., 603950 Nizhny Novgorod, RussiaThe Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Ave., 603950 Nizhny Novgorod, RussiaThe Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Ave., 603950 Nizhny Novgorod, RussiaThe Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Ave., 603950 Nizhny Novgorod, RussiaThe Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Ave., 603950 Nizhny Novgorod, RussiaThe Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Ave., 603950 Nizhny Novgorod, RussiaTumor resistance to therapy is associated with the 3D organization and peculiarities of the tumor microenvironment, of which intercellular adhesion is a key participant. In this work, the abundance of contact proteins was compared in SKOV-3 and SKOV-3.ip human ovarian adenocarcinoma cell lines, cultivated in monolayers, tumor spheroids and collagen hydrogels. Three-dimensional models were characterized by extremely low expression of basic molecules of adherens junctions E-cadherin and demonstrated a simultaneous decrease in desmosomal protein desmoglein-2, gap junction protein connexin-43 and tight junction proteins occludin and ZO-1. The reduction in the level of contact proteins was most pronounced in collagen hydrogel, accompanied by significantly increased resistance to treatment with doxorubicin and targeted anticancer toxin DARPin-LoPE. Thus, we suggest that 3D models of ovarian cancer, especially matrix-based models, tend to recapitulate tumor microenvironment and treatment responsiveness to a greater extent than monolayer culture, so they can be used as a highly relevant platform for drug efficiency evaluation.https://www.mdpi.com/2079-7737/9/12/446cell–cell contactscancer resistancetumor spheroidscollagen hydrogeladherens junctionsdesmosomes
spellingShingle Olga M. Kutova
Ludmila M. Sencha
Anton D. Pospelov
Olga E. Dobrynina
Anna A. Brilkina
Elena I. Cherkasova
Irina V. Balalaeva
Comparative Analysis of Cell–Cell Contact Abundance in Ovarian Carcinoma Cells Cultured in Two- and Three-Dimensional In Vitro Models
Biology
cell–cell contacts
cancer resistance
tumor spheroids
collagen hydrogel
adherens junctions
desmosomes
title Comparative Analysis of Cell–Cell Contact Abundance in Ovarian Carcinoma Cells Cultured in Two- and Three-Dimensional In Vitro Models
title_full Comparative Analysis of Cell–Cell Contact Abundance in Ovarian Carcinoma Cells Cultured in Two- and Three-Dimensional In Vitro Models
title_fullStr Comparative Analysis of Cell–Cell Contact Abundance in Ovarian Carcinoma Cells Cultured in Two- and Three-Dimensional In Vitro Models
title_full_unstemmed Comparative Analysis of Cell–Cell Contact Abundance in Ovarian Carcinoma Cells Cultured in Two- and Three-Dimensional In Vitro Models
title_short Comparative Analysis of Cell–Cell Contact Abundance in Ovarian Carcinoma Cells Cultured in Two- and Three-Dimensional In Vitro Models
title_sort comparative analysis of cell cell contact abundance in ovarian carcinoma cells cultured in two and three dimensional in vitro models
topic cell–cell contacts
cancer resistance
tumor spheroids
collagen hydrogel
adherens junctions
desmosomes
url https://www.mdpi.com/2079-7737/9/12/446
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