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Article

Complex Interplay of Genes Underlies Invasiveness in Fibrosarcoma Progression Model

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Institute of Biology, Faculty of Medicine in Pilsen, Charles University, 323 00 Plzen, Czech Republic
2
Central European Institute of Technology (CEITEC), Masaryk University, 625 00 Brno, Czech Republic
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Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, 602 00 Brno, Czech Republic
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Department of Pathology, University Hospital Brno, 625 00 Brno, Czech Republic
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Internal Medicine V, Medical University of Innsbruck, 6020 Innsbruck, Austria
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Tyrolean Cancer Research Institute, 6020 Innsbruck, Austria
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Department of Medical and Molecular Biology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, 41-808 Zabrze, Poland
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Institute of Physiology, Faculty of Medicine in Pilsen, Charles University, 323 00 Plzen, Czech Republic
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Department of Medical Biology and Genetics, Faculty of Medicine in Hradec Kralove, Charles University, 500 03 Hradec Kralove, Czech Republic
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Biomedical Center, Faculty of Medicine in Pilsen, Charles University, 323 00 Plzen, Czech Republic
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Institute of Pathological Physiology, Faculty of Medicine in Pilsen, Charles University, 323 00 Plzen, Czech Republic
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Institute of Medical Chemistry and Biochemistry, Faculty of Medicine in Pilsen, Charles University, 301 66 Plzen, Czech Republic
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Department of Cybernetics, Faculty of Applied Sciences, University of West Bohemia in Pilsen, 301 00 Plzen, Czech Republic
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Department of Biology, Faculty of Medicine, Masaryk University, 625 00 Brno, Czech Republic
*
Authors to whom correspondence should be addressed.
School of Biotechnology, Devi Ahilya University, Takshashila Campus, Khandwa Road, Indore 452001, MP, India.
Light Microscopy Facility, Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany.
Academic Editor: Rene Rodriguez 
J. Clin. Med. 2021, 10(11), 2297; https://doi.org/10.3390/jcm10112297
Received: 23 April 2021 / Revised: 10 May 2021 / Accepted: 11 May 2021 / Published: 25 May 2021
(This article belongs to the Special Issue Novel Pathogenic Mechanisms and Therapeutic Approaches for Sarcomas)
Sarcomas are a heterogeneous group of mesenchymal tumours, with a great variability in their clinical behaviour. While our knowledge of sarcoma initiation has advanced rapidly in recent years, relatively little is known about mechanisms of sarcoma progression. JUN-murine fibrosarcoma progression series consists of four sarcoma cell lines, JUN-1, JUN-2, JUN-2fos-3, and JUN-3. JUN-1 and -2 were established from a single tumour initiated in a H2K/v-jun transgenic mouse, JUN-3 originates from a different tumour in the same animal, and JUN-2fos-3 results from a targeted in vitro transformation of the JUN-2 cell line. The JUN-1, -2, and -3 cell lines represent a linear progression from the least transformed JUN-2 to the most transformed JUN-3, with regard to all the transformation characteristics studied, while the JUN-2fos-3 cell line exhibits a unique transformation mode, with little deregulation of cell growth and proliferation, but pronounced motility and invasiveness. The invasive sarcoma sublines JUN-2fos-3 and JUN-3 show complex metabolic profiles, with activation of both mitochondrial oxidative phosphorylation and glycolysis and a significant increase in spared respiratory capacity. The specific transcriptomic profile of invasive sublines features very complex biological relationships across the identified genes and proteins, with accentuated autocrine control of motility and angiogenesis. Pharmacologic inhibition of one of the autocrine motility factors identified, Ccl8, significantly diminished both motility and invasiveness of the highly transformed fibrosarcoma cell. This progression series could be greatly valuable for deciphering crucial aspects of sarcoma progression and defining new prognostic markers and potential therapeutic targets. View Full-Text
Keywords: fibrosarcoma; progression series; invasiveness; transcriptome; Ccl8 fibrosarcoma; progression series; invasiveness; transcriptome; Ccl8
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MDPI and ACS Style

Kripnerová, M.; Parmar, H.S.; Šána, J.; Kopková, A.; Radová, L.; Sopper, S.; Biernacki, K.; Jedlička, J.; Kohoutová, M.; Kuncová, J.; Peychl, J.; Rudolf, E.; Červinka, M.; Houdek, Z.; Dvořák, P.; Houfková, K.; Pešta, M.; Tůma, Z.; Dolejšová, M.; Tichánek, F.; Babuška, V.; Leba, M.; Slabý, O.; Hatina, J. Complex Interplay of Genes Underlies Invasiveness in Fibrosarcoma Progression Model. J. Clin. Med. 2021, 10, 2297. https://doi.org/10.3390/jcm10112297

AMA Style

Kripnerová M, Parmar HS, Šána J, Kopková A, Radová L, Sopper S, Biernacki K, Jedlička J, Kohoutová M, Kuncová J, Peychl J, Rudolf E, Červinka M, Houdek Z, Dvořák P, Houfková K, Pešta M, Tůma Z, Dolejšová M, Tichánek F, Babuška V, Leba M, Slabý O, Hatina J. Complex Interplay of Genes Underlies Invasiveness in Fibrosarcoma Progression Model. Journal of Clinical Medicine. 2021; 10(11):2297. https://doi.org/10.3390/jcm10112297

Chicago/Turabian Style

Kripnerová, Michaela, Hamendra S. Parmar, Jiří Šána, Alena Kopková, Lenka Radová, Sieghart Sopper, Krzysztof Biernacki, Jan Jedlička, Michaela Kohoutová, Jitka Kuncová, Jan Peychl, Emil Rudolf, Miroslav Červinka, Zbyněk Houdek, Pavel Dvořák, Kateřina Houfková, Martin Pešta, Zdeněk Tůma, Martina Dolejšová, Filip Tichánek, Václav Babuška, Martin Leba, Ondřej Slabý, and Jiří Hatina. 2021. "Complex Interplay of Genes Underlies Invasiveness in Fibrosarcoma Progression Model" Journal of Clinical Medicine 10, no. 11: 2297. https://doi.org/10.3390/jcm10112297

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