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Complex Interplay of Genes Underlies Invasiveness in Fibrosarcoma Progression Model
M. Kripnerová, HS. Parmar, J. Šána, A. Kopková, L. Radová, S. Sopper, K. Biernacki, J. Jedlička, M. Kohoutová, J. Kuncová, J. Peychl, E. Rudolf, M. Červinka, Z. Houdek, P. Dvořák, K. Houfková, M. Pešta, Z. Tůma, M. Dolejšová, F. Tichánek, V....
Jazyk angličtina Země Švýcarsko
Typ dokumentu časopisecké články
Grantová podpora
PROGRESS Q39
Univerzita Karlova v Praze
PROGRESS Q40/01
Univerzita Karlova v Praze
CZ.02.1.01/0.0/0.0/16_019/0000787
Ministry of Education, Youth and Science
17-17636S
Grantová Agentura České Republiky
260 538/2020
Univerzita Karlova v Praze
260 539/2020
Univerzita Karlova v Praze
LM2018132
Ministry of Education, Youth and Science
NLK
Directory of Open Access Journals
od 2012
Free Medical Journals
od 2012
PubMed Central
od 2012
Europe PubMed Central
od 2012
ProQuest Central
od 2019-01-01
Open Access Digital Library
od 2012-01-01
Open Access Digital Library
od 2012-01-01
Health & Medicine (ProQuest)
od 2019-01-01
ROAD: Directory of Open Access Scholarly Resources
od 2012
PubMed
34070472
DOI
10.3390/jcm10112297
Knihovny.cz E-zdroje
- Publikační typ
- časopisecké články MeSH
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.
Biomedical Center Faculty of Medicine in Pilsen Charles University 323 00 Plzen Czech Republic
Central European Institute of Technology Masaryk University 625 00 Brno Czech Republic
Department of Biology Faculty of Medicine Masaryk University 625 00 Brno Czech Republic
Department of Comprehensive Cancer Care Masaryk Memorial Cancer Institute 602 00 Brno Czech Republic
Department of Pathology University Hospital Brno 625 00 Brno Czech Republic
Institute of Biology Faculty of Medicine in Pilsen Charles University 323 00 Plzen Czech Republic
Institute of Physiology Faculty of Medicine in Pilsen Charles University 323 00 Plzen Czech Republic
Internal Medicine 5 Medical University of Innsbruck 6020 Innsbruck Austria
Citace poskytuje Crossref.org
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- $a 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.
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