NanoRacks-CellBox-Effect of Microgravity on Human Thyroid Carcinoma Cells (NanoRacks-CellBox-Thyroid Cancer) - 05.05.16
Finding new treatments for cancer requires detailed studies of tumor cells, but when cells are grown in a lab on Earth, gravity affects the way they grow and the shapes they take. NanoRacks-CellBox-Effect of Microgravity on Human Thyroid Carcinoma Cells (NanoRacks-CellBox-Thyroid Cancer) studies thyroid cancer cells in microgravity, which enables cells to grow in spheres or in single layers. These unique views of cell structure will be used to look for new biomarkers, which can be used to develop new drugs to treat thyroid cancer. Science Results for Everyone
The Earth is flat – or at least cells grown in laboratories like to be flat. In space, growing cells like to form clusters of spherical cells. To understand why, scientists grew human thyroid cancer cells in space and on the ground. Surprisingly this time, the cells grew flat in both environments, likely because a launch delay allowed buildup of proteins around the cells and anchoring them together flat. This suggests the effects of microgravity can be modified and may explain delayed formation of single-cell-wall tubes in space. Future studies on the response of cancer cells to microgravity could help identify the specific proteins that trigger cell changes in space. Experiment Details
OpNom: BioRack Experiment Containers
Daniela Gabriele Grimm, MD, Institute of Biomedicine, Pharmacology, Aarhus University, Aarhus, Denmark
Jessica Pietsch, Ph.D., Otto-von-Guericke-University Magdeburg, Magdebug, Germany
Stefan Riwaldt, Universitätsklinikum Magdeburg, Magdebug, Germany
Markus Wehland-von Trebra, Ph.D., Otto-von-Guericke-University Magdeburg, Magdebug, Germany
NanoRacks LLC, Webster, TX, United States
EADS Astrium, Friedrichshafen, Germany
Sponsoring Space Agency
National Aeronautics and Space Administration (NASA)
National Laboratory (NL)
Scientific Discovery, Space Exploration, Earth Benefits
ISS Expedition Duration 1
March 2014 - September 2014
Previous ISS Missions
NanoRacks-CellBox-Effect of Microgravity on Human Thyroid Carcinoma Cells (NanoRacks-CellBox-Thyroid Cancer) investigates the effects of microgravity on human thyroid cancer cells.
The goal is to possibly identify new biomarkers in the genome (hereditary information), the proteome (expressed proteins) or the secretome (secreted proteins) which could be used to develop new thyorid cancer drugs or to gain a better understanding of the mechanism leading to cancer development and thus to new strategies of thyroid cancer therapy.
The principle aim of NanoRacks-CellBox-Effect of Microgravity on Human Thyroid Carcinoma Cells (NanoRacks-CellBox-Thyroid Cancer) is to investigate the effects of real microgravity on human thyroid carcinoma cells (FTC-133 cell line). Data obtained from this experiment is compared to the thyroid cancer cells characterized after exposure to simulated microgravity and after the successful SIMBOX on Shenzhou-8 mission (2011, Experiment 14).
Single cancer cells of the FTC-133 cell line are cultured during NanoRacks-CellBox-Thyroid Cancer) investigation. The cells are expected to form three-dimensional multicellular tumor spheroids (MCTS), which clearly resemble the respective originating tumor. Under conditions of microgravity, cells keep floating without stirring so that initial cell-cell interactions required for spheroid formation are induced by forces only due to biochemical components actually expressed on surfaces of cells but gravity related push and shear events do not influence MCTS formation. After the SIMBOX mission, it was shown for the first time that FTC-133 cells grew in form of 3D multicellular spheroids and also adherently as a monolayer in space. Epidermal growth factor (EGF) and connective tissue growth factor (CTGF) may be involved in 3D aggregation in space. The secretion of cytokines was down-regulated in space. The inducers of tumor neoangiogenesis OPN, IL-6, IL-8, and VEGF-a were all reduced under real microgravity. Several gravisensitive signaling elements, such as protein kinases A and C as well as integrins, are involved in the reaction of thyroid cancer cells to microgravity. The increase in VEGF-d secretion of the original low differentiated thyroid cancer cells indicated a redifferentiation of these cells in space. The hope is to confirm these findings and thus increase the number of experiments for statistical reasons. The overall aim of the studies in microgravity is the identification of new biomarkers which can be used for developing new cancer drugs.^ back to top
Certain cell receptors and cell signaling mechanisms work differently in space, which affects how cancer cells grow. Microgravity enables cells to form three-dimensional clumps, which can be used to study tumor formation and to search for biological markers. These methods for studying cancer would not be possible in Earth’s gravity, making the International Space Station a unique laboratory for studying cancer.
Thyroid cancer is the fastest-increasing cancer in the United States, mostly because new technology is allowing doctors to find it more easily, according to the American Cancer Society. Results from this investigation may reveal new biological markers for thyroid cancer, which could be used to develop new drugs to treat it.
Operational Requirements and Protocols
BioRack Experiment Containers are returned at 4°C.
A crewmember installs BioRack Experiment Containers no later than docking plus two days. After automatic fixation, the containers must remain in the BioRack for a minimum of 12 days prior to the crewmember removing and storing at 4°C for return.^ back to top
Decadal Survey Recommendations
Information Pending^ back to top
In microgravity, many types of cells grow as a cluster of round cells rather than a sheet of flat cells as on earth. In an attempt to understand this behavior, scientists investigate the protein content and growth pattern of cells grown in both environments. Surprisingly, human thyroid cancer cells samples returned from the International Space Station (ISS) show no visual physical differences from the ground-control cultures. Protein analysis did not indicate significant differences between cells exposed to microgravity and their 1g controls, but suggest that an enhanced production of proteins surrounding the cells and a membrane protein caveolin-1, could possibly prevent them from spheroid formation. It is hypothesized that the unexpected result of the thyroid cancer cells not forming spheroids during their stay on the ISS is very likely due to a launch delay. The prolonged pre-incubation of the cells increases extracellular matrix (ECM) proteins. It appears likely that a firm anchorage of ECM proteins in the cellular sheet could prevent spheroid formation. At the moment, it is not certain whether the observation is due only to a high cell density or also to up-or down-regulated cell components during the extended incubation period on ground. This finding is of high interest, because it shows possibilities to modify the effects of microgravity and may also explain why the formation of tubes surrounded by a single cell wall is delayed. Future comparative studies on cancer cells, which do or do not form spheroids when exposed to microgravity, may help to identify those proteins that trigger cellular alterations under microgravity.^ back to top
Riwaldt S, Pietsch J, Sickmann A, Bauer J, Braun M, Segerer J, Schwarzwälder A, Aleshcheva G, Corydon TJ, Infanger M, Grimm DG. Identification of proteins involved in inhibition of spheroid formation under microgravity. Proteomics. 2015 April 29; epub. DOI: 10.1002/pmic.201500067. PMID: 25930030.
Riwaldt S, Bauer J, Pietsch J, Braun M, Segerer J, Schwarzwälder A, Corydon TJ, Infanger M, Grimm DG. The importance of Caveolin-1 as key-regulator of three-dimensional growth in thyroid cancer cells cultured under real and simulated microgravity conditions. International Journal of Molecular Sciences. 2015 November 30; 16(12): 28296-28310. DOI: 10.3390/ijms161226108. PMID: 26633361.
Ground Based Results Publications