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  Pathways Regulating Spheroid Formation of Human Follicular Thyroid Cancer Cells under Simulated Microgravity Conditions: A Genetic Approach

Riwaldt, S., Bauer, J., Wehland, M., Slumstrup, L., Kopp, S., Warnke, E., et al. (2016). Pathways Regulating Spheroid Formation of Human Follicular Thyroid Cancer Cells under Simulated Microgravity Conditions: A Genetic Approach. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 17(4): 528. doi:10.3390/ijms17040528.

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 Creators:
Riwaldt, Stefan1, Author
Bauer, Johann2, Author              
Wehland, Markus1, Author
Slumstrup, Lasse1, Author
Kopp, Sascha1, Author
Warnke, Elisabeth1, Author
Dittrich, Anita1, Author
Magnusson, Nils E.1, Author
Pietsch, Jessica1, Author
Corydon, Thomas J.1, Author
Infanger, Manfred1, Author
Grimm, Daniela1, Author
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1external, ou_persistent22              
2Scientific Service Groups, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565170              

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Free keywords: ENDOTHELIAL-GROWTH-FACTOR; PROTEIN-KINASE-C; 3-DIMENSIONAL GROWTH; IN-VITRO; KAPPA-B; VEGF-A; EXPRESSION; CARCINOMA; SPACE; LINEthyroid cancer; simulated microgravity; random positioning machine; pathway studio; caveolin-1; vascular endothelial growth factor; matrix metalloproteinases; growth;
 Abstract: Microgravity induces three-dimensional (3D) growth in numerous cell types. Despite substantial efforts to clarify the underlying mechanisms for spheroid formation, the precise molecular pathways are still not known. The principal aim of this paper is to compare static 1g-control cells with spheroid forming (MCS) and spheroid non-forming (AD) thyroid cancer cells cultured in the same flask under simulated microgravity conditions. We investigated the morphology and gene expression patterns in human follicular thyroid cancer cells (UCLA RO82-W-1 cell line) after a 24 h-exposure on the Random Positioning Machine (RPM) and focused on 3D growth signaling processes. After 24 h, spheroid formation was observed in RPM-cultures together with alterations in the F-actin cytoskeleton. qPCR indicated more changes in gene expression in MCS than in AD cells. Of the 24 genes analyzed VEGFA, VEGFD, MSN, and MMP3 were upregulated in MCS compared to 1g-controls, whereas ACTB, ACTA2, KRT8, TUBB, EZR, RDX, PRKCA, CAV1, MMP9, PAI1, CTGF, MCP1 were downregulated. A pathway analysis revealed that the upregulated genes code for proteins, which promote 3D growth (angiogenesis) and prevent excessive accumulation of extracellular proteins, while genes coding for structural proteins are downregulated. Pathways regulating the strength/rigidity of cytoskeletal proteins, the amount of extracellular proteins, and 3D growth may be involved in MCS formation.

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Language(s): eng - English
 Dates: 2016
 Publication Status: Published online
 Pages: 20
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: ISI: 000374585300107
DOI: 10.3390/ijms17040528
 Degree: -

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Title: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Source Genre: Journal
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Publ. Info: POSTFACH, CH-4005 BASEL, SWITZERLAND : MDPI AG
Pages: - Volume / Issue: 17 (4) Sequence Number: 528 Start / End Page: - Identifier: ISSN: 1422-0067