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Kripnerova 2021 J Clin Med

From Bioblast
Publications in the MiPMap
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 (2021) Complex interplay of genes underlies invasiveness in fibrosarcoma progression model. J Clin Med 10:2297.

» PMID: 34070472 Open Access

Kripnerova Michaela, Singh Parmar Hamendra, Sana Jiri, Kopkova Alena, Radova Lenka, Sopper Sieghart, Biernacki Krzysztof, Jedlicka Jan, Kohoutova Michaela, Kuncova Jitka, Peychl Jan, Rudolf Emil, Cervinka Miroslav, Houdek Zbynek, Dvorak Pavel, Houfkova Katerina, Pesta Martin, Tuma Zdenek, Dolejsova Martina, Tichanek Filip, Babuska Vaclav, Leba Martin, Slaby Ondrej, Hatina Jiri (2021) J Clin Med

Abstract: 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. Keywords: Ccl8, Fibrosarcoma, Invasiveness, Progression series, Transcriptome Bioblast editor: Plangger M O2k-Network Lab: CZ Pilsen Kuncova J, CZ Hradec Kralove Cervinkova Z

Labels: MiParea: Respiration  Pathology: Cancer 

Organism: Mouse  Tissue;cell: Fibroblast  Preparation: Intact cells 

Coupling state: LEAK, ROUTINE, ET  Pathway: ROX  HRR: Oxygraph-2k