Malignant Ascites Promote Adhesion of Ovarian Cancer Cells to Peritoneal Mesothelium and Fibroblasts

Although malignant ascites (MAs) are known to contribute to various aspects of ovarian cancer progression, knowledge regarding their role in the adhesion of cancer cells to normal peritoneal cells is incomplete. Here, we compared the effect of MAs and benign ascites (BAs) on the adhesion of A2780 an...

Full description

Bibliographic Details
Main Authors: Paweł Uruski, Justyna Mikuła-Pietrasik, Martyna Pakuła, Sylwia Budkiewicz, Marcin Drzewiecki, Andrey N. Gaiday, Małgorzata Wierzowiecka, Eryk Naumowicz, Rafał Moszyński, Andrzej Tykarski, Krzysztof Książek
Format: Article
Language:English
Published: MDPI AG 2021-04-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/22/8/4222
_version_ 1797537102732197888
author Paweł Uruski
Justyna Mikuła-Pietrasik
Martyna Pakuła
Sylwia Budkiewicz
Marcin Drzewiecki
Andrey N. Gaiday
Małgorzata Wierzowiecka
Eryk Naumowicz
Rafał Moszyński
Andrzej Tykarski
Krzysztof Książek
author_facet Paweł Uruski
Justyna Mikuła-Pietrasik
Martyna Pakuła
Sylwia Budkiewicz
Marcin Drzewiecki
Andrey N. Gaiday
Małgorzata Wierzowiecka
Eryk Naumowicz
Rafał Moszyński
Andrzej Tykarski
Krzysztof Książek
author_sort Paweł Uruski
collection DOAJ
description Although malignant ascites (MAs) are known to contribute to various aspects of ovarian cancer progression, knowledge regarding their role in the adhesion of cancer cells to normal peritoneal cells is incomplete. Here, we compared the effect of MAs and benign ascites (BAs) on the adhesion of A2780 and OVCAR-3 cancer cells to omentum-derived peritoneal mesothelial cells (PMCs) and peritoneal fibroblasts (PFBs). The results showed that MAs stimulated the adhesion of A2780 and OVCAR-3 cells to PMCs and PFBs more efficiently than did BAs, and the strongest binding occurred when both cancer and normal cells were exposed to the fluid. Intervention studies showed that MAs-driven adhesion of A2780 cells to PMCs/PFBs depends on the presence of TGF-β1 and HGF, whereas binding of OVCAR-3 cells was mediated by TGF-β1, GRO-1, and IGF-1. Moreover, MAs upregulated α5β1 integrin expression on PFBs but not on PMCs or cancer cells, vimentin expression in all cells tested, and ICAM-1 only in cancer cells. When integrin-linked kinase was neutralized in PMCs or PFBs, cancer cell adhesion to PMCs and PFBs decreased. Collectively, our report shows that MAs may contribute to the early stages of ovarian cancer metastasis by modulating the proadhesive interplay between normal and cancer cells.
first_indexed 2024-03-10T12:11:14Z
format Article
id doaj.art-1b89f7f2dd4147c9a08a7f438c58a4c4
institution Directory Open Access Journal
issn 1661-6596
1422-0067
language English
last_indexed 2024-03-10T12:11:14Z
publishDate 2021-04-01
publisher MDPI AG
record_format Article
series International Journal of Molecular Sciences
spelling doaj.art-1b89f7f2dd4147c9a08a7f438c58a4c42023-11-21T16:12:16ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-04-01228422210.3390/ijms22084222Malignant Ascites Promote Adhesion of Ovarian Cancer Cells to Peritoneal Mesothelium and FibroblastsPaweł Uruski0Justyna Mikuła-Pietrasik1Martyna Pakuła2Sylwia Budkiewicz3Marcin Drzewiecki4Andrey N. Gaiday5Małgorzata Wierzowiecka6Eryk Naumowicz7Rafał Moszyński8Andrzej Tykarski9Krzysztof Książek10Department of Hypertensiology, Poznan University of Medical Sciences, Długa 1/2 Str., 61-848 Poznan, PolandDepartment of Pathophysiology of Ageing and Civilization Diseases, Poznan University of Medical Sciences, Długa 1/2 Str., 61-848 Poznan, PolandDepartment of Hypertensiology, Poznan University of Medical Sciences, Długa 1/2 Str., 61-848 Poznan, PolandDepartment of Pathophysiology of Ageing and Civilization Diseases, Poznan University of Medical Sciences, Długa 1/2 Str., 61-848 Poznan, PolandDepartment of Pathophysiology of Ageing and Civilization Diseases, Poznan University of Medical Sciences, Długa 1/2 Str., 61-848 Poznan, PolandDepartment of Obstetrics and Gynecology, West Kazakhstan Marat Ospanov Medical University, 50B 12th Microdistrict Apt.21, Aktobe 030008, KazakhstanDepartment of Hypertensiology, Poznan University of Medical Sciences, Długa 1/2 Str., 61-848 Poznan, PolandGeneral Surgery Ward, Medical Centre HCP, 28 Czerwca 1956 r. 223/229 Str., 61-485 Poznan, PolandDivision of Gynecological Surgery, Poznan University of Medical Sciences, Polna 33 Str., 60-535 Poznan, PolandDepartment of Hypertensiology, Poznan University of Medical Sciences, Długa 1/2 Str., 61-848 Poznan, PolandDepartment of Pathophysiology of Ageing and Civilization Diseases, Poznan University of Medical Sciences, Długa 1/2 Str., 61-848 Poznan, PolandAlthough malignant ascites (MAs) are known to contribute to various aspects of ovarian cancer progression, knowledge regarding their role in the adhesion of cancer cells to normal peritoneal cells is incomplete. Here, we compared the effect of MAs and benign ascites (BAs) on the adhesion of A2780 and OVCAR-3 cancer cells to omentum-derived peritoneal mesothelial cells (PMCs) and peritoneal fibroblasts (PFBs). The results showed that MAs stimulated the adhesion of A2780 and OVCAR-3 cells to PMCs and PFBs more efficiently than did BAs, and the strongest binding occurred when both cancer and normal cells were exposed to the fluid. Intervention studies showed that MAs-driven adhesion of A2780 cells to PMCs/PFBs depends on the presence of TGF-β1 and HGF, whereas binding of OVCAR-3 cells was mediated by TGF-β1, GRO-1, and IGF-1. Moreover, MAs upregulated α5β1 integrin expression on PFBs but not on PMCs or cancer cells, vimentin expression in all cells tested, and ICAM-1 only in cancer cells. When integrin-linked kinase was neutralized in PMCs or PFBs, cancer cell adhesion to PMCs and PFBs decreased. Collectively, our report shows that MAs may contribute to the early stages of ovarian cancer metastasis by modulating the proadhesive interplay between normal and cancer cells.https://www.mdpi.com/1422-0067/22/8/4222cancer cell adhesionmalignant ascitesovarian cancerperitoneal metastases
spellingShingle Paweł Uruski
Justyna Mikuła-Pietrasik
Martyna Pakuła
Sylwia Budkiewicz
Marcin Drzewiecki
Andrey N. Gaiday
Małgorzata Wierzowiecka
Eryk Naumowicz
Rafał Moszyński
Andrzej Tykarski
Krzysztof Książek
Malignant Ascites Promote Adhesion of Ovarian Cancer Cells to Peritoneal Mesothelium and Fibroblasts
International Journal of Molecular Sciences
cancer cell adhesion
malignant ascites
ovarian cancer
peritoneal metastases
title Malignant Ascites Promote Adhesion of Ovarian Cancer Cells to Peritoneal Mesothelium and Fibroblasts
title_full Malignant Ascites Promote Adhesion of Ovarian Cancer Cells to Peritoneal Mesothelium and Fibroblasts
title_fullStr Malignant Ascites Promote Adhesion of Ovarian Cancer Cells to Peritoneal Mesothelium and Fibroblasts
title_full_unstemmed Malignant Ascites Promote Adhesion of Ovarian Cancer Cells to Peritoneal Mesothelium and Fibroblasts
title_short Malignant Ascites Promote Adhesion of Ovarian Cancer Cells to Peritoneal Mesothelium and Fibroblasts
title_sort malignant ascites promote adhesion of ovarian cancer cells to peritoneal mesothelium and fibroblasts
topic cancer cell adhesion
malignant ascites
ovarian cancer
peritoneal metastases
url https://www.mdpi.com/1422-0067/22/8/4222
work_keys_str_mv AT pawełuruski malignantascitespromoteadhesionofovariancancercellstoperitonealmesotheliumandfibroblasts
AT justynamikułapietrasik malignantascitespromoteadhesionofovariancancercellstoperitonealmesotheliumandfibroblasts
AT martynapakuła malignantascitespromoteadhesionofovariancancercellstoperitonealmesotheliumandfibroblasts
AT sylwiabudkiewicz malignantascitespromoteadhesionofovariancancercellstoperitonealmesotheliumandfibroblasts
AT marcindrzewiecki malignantascitespromoteadhesionofovariancancercellstoperitonealmesotheliumandfibroblasts
AT andreyngaiday malignantascitespromoteadhesionofovariancancercellstoperitonealmesotheliumandfibroblasts
AT małgorzatawierzowiecka malignantascitespromoteadhesionofovariancancercellstoperitonealmesotheliumandfibroblasts
AT eryknaumowicz malignantascitespromoteadhesionofovariancancercellstoperitonealmesotheliumandfibroblasts
AT rafałmoszynski malignantascitespromoteadhesionofovariancancercellstoperitonealmesotheliumandfibroblasts
AT andrzejtykarski malignantascitespromoteadhesionofovariancancercellstoperitonealmesotheliumandfibroblasts
AT krzysztofksiazek malignantascitespromoteadhesionofovariancancercellstoperitonealmesotheliumandfibroblasts