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Title: The effects of real and simulated microgravity on human cancer cells
Author(s): Kopp, Sascha
Referee(s): Stannarius, Ralf
Anken, Ralf
Granting Institution: Otto-von-Guericke-Universität Magdeburg
Issue Date: 2018
Extent: 1 Online-Ressource (PDF-Datei: verschiedene Seitenzählung, 5,24 MB)
Type: Hochschulschrift
Type: Doctoral thesis
Exam Date: 2018
Language: English
Publisher: Otto von Guericke University Library, Magdeburg, Germany
URN: urn:nbn:de:gbv:ma9:1-1981185920-13714.28
Subjects: Krebszelle
cancer cells
Abstract: Since NASA announced their plans to take mankind deeper into space, the need to understand the basic reaction of human cells to the altered gravity environment has increased. Generally, it is hypothesized that human cells sense gravity changes via the cytoskeleton. However, live cell imaging was not possible until now. In addition, various cell types cultured under microgravity conditions grew in the form of multicellular spheroids (MCS). These MCS often closely resemble the in vivo tissue from which they originate. This thesis includes four publications highlighting cytoskeletal alterations in cancer cells under altered gravity conditions, as well as, the formation and the mechanisms of MCS growth in thyroid- and breast cancer cells. The first paper focused on the development of a compact fluorescence microscope (FLUMIAS) for fast live-cell imaging in real microgravity. For the first time, the F-actin cytoskeleton was visualized in living Lifeact-GFP expressing follicular thyroid cancer cells (FTC-133) in response to microgravity. The second paper investigated the early changes in gene expression of follicular thyroid cancer cells exposed to the RPM. The genes were regulated in a pro-angiogenic manner in MCS compared to controls. Driven by the hypothesis that cells form tissue-specific MCS under microgravity conditions, MCF-7 breast cancer cells were exposed to the RPM. After a five-day RPM-exposure, the majority of MCS presented a cell-free lumen resembling ducts formed in vivo by human epithelial breast cells. Pathway analyses revealed involvement in the organization and regulation of cell shape, cell tip formation and membrane-to-membrane docking (Paper 3). Paper number 4 demonstrated the importance of NF-κB for MCS formation in RPM-exposed MCF-7 cells. An interaction analysis of 47 investigated genes suggested that HMOX-1, ICAM1 and NF-κB variants are activated when multicellular spheroids are formed. In addition, the application of NF-κB inhibitors resulted in a decrease in MCS formation.
Open Access: Open access publication
License: (CC BY-SA 4.0) Creative Commons Attribution ShareAlike 4.0(CC BY-SA 4.0) Creative Commons Attribution ShareAlike 4.0
Appears in Collections:Medizinische Fakultät

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