Versican modulates tumor-associated macrophage properties to stimulate mesothelioma growth
Versican promotes experimental tumor growth through cell- and non cell-autonomous mechanisms. Its role in mesothelioma progression has not been investigated so far. In this study we investigated the impact of tumor-derived versican in mesothelioma progression and the underlying mechanism of its acti...
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doaj-ba3759eb488e464e890ed0b093da87df2020-11-25T02:36:56ZengTaylor & Francis GroupOncoImmunology2162-402X2019-02-018210.1080/2162402X.2018.15374271537427Versican modulates tumor-associated macrophage properties to stimulate mesothelioma growthApostolos G. Pappas0Sophia Magkouta1Ioannis S. Pateras2Ioannis Skianis3Charalampos Moschos4Maria Eleni Vazakidou5Katherina Psarra6Vassilis G. Gorgoulis7Ioannis Kalomenidis8National and Kapodistrian University of Athens, School of Medicine, “Evangelismos” HospitalNational and Kapodistrian University of Athens, School of Medicine, “Evangelismos” HospitalNational & Kapodistrian University of AthensAthens University of Economic & BusinessNational and Kapodistrian University of Athens, School of Medicine, “Evangelismos” HospitalNational and Kapodistrian University of Athens, School of Medicine, “Evangelismos” HospitalDepartment of Immunology - Histocompatibility, “Evangelismos” HospitalNational & Kapodistrian University of AthensNational and Kapodistrian University of Athens, School of Medicine, “Evangelismos” HospitalVersican promotes experimental tumor growth through cell- and non cell-autonomous mechanisms. Its role in mesothelioma progression has not been investigated so far. In this study we investigated the impact of tumor-derived versican in mesothelioma progression and the underlying mechanism of its action. For this purpose, versican-silenced or control ΑΕ17 and ΑΒ1 murine mesothelioma cells were intrapleuraly injected into syngeneic mice, in order to create pleural mesotheliomas and pleural effusions. Intratumoral and pleural immune subsets were assessed using flow cytometry. Mesothelioma cells were co-cultured with syngeneic macrophages to examine versican’s impact on their interaction and endothelial cells to assess the effect of versican in endothelial permeability. Versican expression was assessed in human mesotheliomas and mesothelioma-related pleural effusions and benign pleural tissue and effusions. We observed that, versican silencing reduced mesothelioma mass and pleural fluid volume by affecting tumor cell proliferation and apoptosis in vivo, while tumor cell growth remained intact in vitro, and limited pleural vascular permeability. Mice harboring versican-deficient tumors presented fewer tumor/pleural macrophages and neutrophils, and fewer pleural T-regulatory cells, compared to the control animals. Macrophages co-cultured with versican-deficient mesothelioma cells were polarized towards M1 anti-tumor phenotype and demonstrated increased tumor cell phagocytic capacity, compared to macrophages co-cultured with control tumor cells. In co-culture, endothelial monolayer permeability was less effectively stimulated by versican-deficient cells than control cells. Versican was over-expressed in human mesothelioma tissue and mesothelioma-associated effusion. In conclusion, tumor cell-derived versican stimulates mesothelioma progression by shaping a tumor friendly inflammatory milieu, mainly by blunting macrophage anti-tumor activities.http://dx.doi.org/10.1080/2162402X.2018.1537427chondroitin sulfate proteoglycan core protein 2pleural neoplasmsmonocytes/macrophagesextra-cellular matrixtumor-immunology |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Apostolos G. Pappas Sophia Magkouta Ioannis S. Pateras Ioannis Skianis Charalampos Moschos Maria Eleni Vazakidou Katherina Psarra Vassilis G. Gorgoulis Ioannis Kalomenidis |
spellingShingle |
Apostolos G. Pappas Sophia Magkouta Ioannis S. Pateras Ioannis Skianis Charalampos Moschos Maria Eleni Vazakidou Katherina Psarra Vassilis G. Gorgoulis Ioannis Kalomenidis Versican modulates tumor-associated macrophage properties to stimulate mesothelioma growth OncoImmunology chondroitin sulfate proteoglycan core protein 2 pleural neoplasms monocytes/macrophages extra-cellular matrix tumor-immunology |
author_facet |
Apostolos G. Pappas Sophia Magkouta Ioannis S. Pateras Ioannis Skianis Charalampos Moschos Maria Eleni Vazakidou Katherina Psarra Vassilis G. Gorgoulis Ioannis Kalomenidis |
author_sort |
Apostolos G. Pappas |
title |
Versican modulates tumor-associated macrophage properties to stimulate mesothelioma growth |
title_short |
Versican modulates tumor-associated macrophage properties to stimulate mesothelioma growth |
title_full |
Versican modulates tumor-associated macrophage properties to stimulate mesothelioma growth |
title_fullStr |
Versican modulates tumor-associated macrophage properties to stimulate mesothelioma growth |
title_full_unstemmed |
Versican modulates tumor-associated macrophage properties to stimulate mesothelioma growth |
title_sort |
versican modulates tumor-associated macrophage properties to stimulate mesothelioma growth |
publisher |
Taylor & Francis Group |
series |
OncoImmunology |
issn |
2162-402X |
publishDate |
2019-02-01 |
description |
Versican promotes experimental tumor growth through cell- and non cell-autonomous mechanisms. Its role in mesothelioma progression has not been investigated so far. In this study we investigated the impact of tumor-derived versican in mesothelioma progression and the underlying mechanism of its action. For this purpose, versican-silenced or control ΑΕ17 and ΑΒ1 murine mesothelioma cells were intrapleuraly injected into syngeneic mice, in order to create pleural mesotheliomas and pleural effusions. Intratumoral and pleural immune subsets were assessed using flow cytometry. Mesothelioma cells were co-cultured with syngeneic macrophages to examine versican’s impact on their interaction and endothelial cells to assess the effect of versican in endothelial permeability. Versican expression was assessed in human mesotheliomas and mesothelioma-related pleural effusions and benign pleural tissue and effusions. We observed that, versican silencing reduced mesothelioma mass and pleural fluid volume by affecting tumor cell proliferation and apoptosis in vivo, while tumor cell growth remained intact in vitro, and limited pleural vascular permeability. Mice harboring versican-deficient tumors presented fewer tumor/pleural macrophages and neutrophils, and fewer pleural T-regulatory cells, compared to the control animals. Macrophages co-cultured with versican-deficient mesothelioma cells were polarized towards M1 anti-tumor phenotype and demonstrated increased tumor cell phagocytic capacity, compared to macrophages co-cultured with control tumor cells. In co-culture, endothelial monolayer permeability was less effectively stimulated by versican-deficient cells than control cells. Versican was over-expressed in human mesothelioma tissue and mesothelioma-associated effusion. In conclusion, tumor cell-derived versican stimulates mesothelioma progression by shaping a tumor friendly inflammatory milieu, mainly by blunting macrophage anti-tumor activities. |
topic |
chondroitin sulfate proteoglycan core protein 2 pleural neoplasms monocytes/macrophages extra-cellular matrix tumor-immunology |
url |
http://dx.doi.org/10.1080/2162402X.2018.1537427 |
work_keys_str_mv |
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