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Gravity-sensitive signaling drives 3-dimensional formation of multicellular thyroid cancer spheroids

Item Type:Article
Title:Gravity-sensitive signaling drives 3-dimensional formation of multicellular thyroid cancer spheroids
Creators Name:Grosse, J. and Wehland, M. and Pietsch, J. and Schulz, H. and Saar, K. and Huebner, N. and Eilles, C. and Bauer, J. and Abou-El-Ardat, K. and Baatout, S. and Ma, X. and Infanger, M. and Hemmersbach, R. and Grimm, D.
Abstract:This study focused on the effects induced by a random positioning machine (RPM) on FTC-133 thyroid cancer cells and evaluated signaling elements involved in 3-dimensional multicellular tumor spheroid (MCTS) formation. The cells were cultured on the RPM, a device developed to simulate microgravity, and under static 1-g conditions. After 24 h on the RPM, MCTSs swimming in culture supernatants were found, in addition to growth of adherent (AD) cells. Cells grown on the RPM showed higher levels of NF-{kappa}B p65 protein and apoptosis than 1-g controls, a result also found earlier in endothelial cells. Employing microarray analysis, we found 487 significantly regulated transcripts belonging not only to the apoptosis pathway but also to other biological processes. Selected transcripts were analyzed with quantitative real-time PCR using the same samples. Compared with 1-g IL-6, IL-8, CD44, and OPN were significantly up-regulated in AD cells but not in MCTSs, while ERK1/2, CAV2, TLN1, and CTGF were significantly down-regulated in AD cells. Simultaneously, the expression of ERK2, IL-6, CAV2, TLN1, and CTGF was reduced in MCTSs. IL-6 protein expression and secretion mirrored its gene expression. Thus, we concluded that the signaling elements IL-6, IL-8, OPN, TLN1, and CTGF are involved with NF-{KAPPA}B p65 in RPM-dependent thyroid carcinoma cell spheroid formation.
Keywords:Gene Expression, Simulated Microgravity, Cytokines, Neoangiogenesis
Source:FASEB Journal
Publisher:Federation of American Societies for Experimental Biology
Page Range:5124-5140
Date:December 2012
Official Publication:https://doi.org/10.1096/fj.12-215749
PubMed:View item in PubMed

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