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A Unique Pattern of Mesothelial-Mesenchymal Transition Induced in the Normal Peritoneal Mesothelium by High-Grade Serous Ovarian Cancer

1
Department of Hypertensiology, Angiology and Internal Medicine, Poznan University of Medical Sciences, Długa 1/2 Str., 61-848 Poznan, Poland
2
Department of Clinical Pathology, Poznan University of Medical Sciences, Przybyszewskiego 49 Str., 60-355 Poznan, Poland
3
Division of Gynecological Surgery, Poznan University of Medical Sciences, Polna 33 Str, 60-535 Poznan, Poland
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(5), 662; https://doi.org/10.3390/cancers11050662
Received: 13 April 2019 / Revised: 7 May 2019 / Accepted: 13 May 2019 / Published: 13 May 2019
(This article belongs to the Special Issue Cancer Invasion and Metastasis)
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Abstract

The study was designed to establish whether high aggressiveness of high-grade serous ovarian cancer cells (HGSOCs), which display rapid growth, advanced stage at diagnosis and the highest mortality among all epithelial ovarian cancer histotypes, may be linked with a specific pattern of mesothelial-mesenchymal transition (MMT) elicited by these cells in normal peritoneal mesothelial cells (PMCs). Experiments were performed on primary PMCs, stable and primary ovarian cancer cells, tumors from patients with ovarian cancer, and laboratory animals. Results of in vitro and in vivo tests showed that MMT triggered by HGSOCs (primary cells and OVCAR-3 line) is far more pronounced than the process evoked by cells representing less aggressive ovarian cancer histotypes (A2780, SKOV-3). Mechanistically, HGSOCs induce MMT via Smad 2/3, ILK, TGF-β1, HGF, and IGF-1, whereas A2780 and SKOV-3 cells via exclusively Smad 2/3 and HGF. The conditioned medium from PMCs undergoing MMT promoted the progression of cancer cells and the effects exerted by the cells triggered to undergo MMT by the HGSOCs were significantly stronger than those related to the activity of their less aggressive counterparts. Our findings indicate that MMT in PMCs provoked by HGSOCs is stronger, proceeds via different mechanisms and has more procancerous characteristics than MMT provoked by less aggressive cancer histotypes, which may at least partly explain high aggressiveness of HGSOCs. View Full-Text
Keywords: cancer metastases; mesothelial cells; mesothelial-mesenchymal transition; ovarian cancer; peritoneal cavity cancer metastases; mesothelial cells; mesothelial-mesenchymal transition; ovarian cancer; peritoneal cavity
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Pakuła, M.; Uruski, P.; Niklas, A.; Woźniak, A.; Szpurek, D.; Tykarski, A.; Mikuła-Pietrasik, J.; Książek, K. A Unique Pattern of Mesothelial-Mesenchymal Transition Induced in the Normal Peritoneal Mesothelium by High-Grade Serous Ovarian Cancer. Cancers 2019, 11, 662.

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