Tumors in Space: Preparation for Spaceflight

Larose, Tricia L

doi:10.5772/intechopen.93465

Cited by 4 publications

(5 citation statements)

References 20 publications

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“…The LET values of the applied beams were 10 keV/µm for protons and 65 keV/µm for alphas. Detailed description of the track segment irradiation platform and its operational principles can be found elsewhere [1][2][3][4] . We will state here only the main features of the irradiation protocol.…”

Section: Cell Irradiation Culture and Clone Isolationmentioning

confidence: 99%

“…Humans have a keen interest in travelling in space, from deep space exploration to extraterrestrial colonization. In addition, the space environment was also considered for biomedical research purposes, for example the “tumors in space” experiment aims to study the effects of microgravity and exposure to space radiation on tumor organoids 1 . Spaceflight is usually defined as crossing the Kármán separation line i.e.…”

Section: Introductionmentioning

confidence: 99%

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Proton and alpha radiation-induced mutational profiles in human cells

Delhomme

Munteanu

Grilj

et al. 2023

Sci Rep

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Ionizing radiation is known to be DNA damaging and mutagenic, however less is known about which mutational footprints result from exposures of human cells to different types of radiation. We were interested in the mutagenic effects of particle radiation exposures on genomes of various human cell types, in order to gauge the genotoxic risks of galactic cosmic radiation, and of certain types of tumor radiotherapy. To this end, we exposed cultured cell lines from the human blood, breast and lung to fractionated proton and alpha particle (helium nuclei) beams at doses sufficient to considerably affect cell viability. Whole-genome sequencing revealed that mutation rates were not overall markedly increased upon proton and alpha exposures. However, there were modest changes in mutation spectra and distributions, such as the increases in clustered mutations and of certain types of indels and structural variants. The spectrum of mutagenic effects of particle beams may be cell-type and/or genetic background specific. Overall, the mutational effects of repeated exposures to proton and alpha radiation on human cells in culture appear subtle, however further work is warranted to understand effects of long-term exposures on various human tissues.

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Section: Cell Irradiation Culture and Clone Isolationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Proton and alpha radiation-induced mutational profiles in human cells

Delhomme

Munteanu

Grilj

et al. 2023

Sci Rep

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“…One possible approach to answering this ambiguous question is the planned project by Larose and colleagues to study spheroids and organoids under real microgravity conditions. This will open up the possibility of testing the extent to which microgravity affects the three-dimensional constructs of cancer cells [62].…”

Section: Cell Modelsmentioning

confidence: 99%

Fluid and Bubble Flow Detach Adherent Cancer Cells to Form Spheroids on a Random Positioning Machine

Cortés-Sánchez,

Melnik,

Sandt

et al. 2023

Cells

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In preparing space and microgravity experiments, the utilization of ground-based facilities is common for initial experiments and feasibility studies. One approach to simulating microgravity conditions on Earth is to employ a random positioning machine (RPM) as a rotary bioreactor. Combined with a suitable low-mass model system, such as cell cultures, these devices simulating microgravity have been shown to produce results similar to those obtained in a space experiment under real microgravity conditions. One of these effects observed under real and simulated microgravity is the formation of spheroids from 2D adherent cancer cell cultures. Since real microgravity cannot be generated in a laboratory on Earth, we aimed to determine which forces lead to the detachment of individual FTC-133 thyroid cancer cells and the formation of tumor spheroids during culture with exposure to random positioning modes. To this end, we subdivided the RPM motion into different static and dynamic orientations of cell culture flasks. We focused on the molecular activation of the mechanosignaling pathways previously associated with spheroid formation in microgravity. Our results suggest that RPM-induced spheroid formation is a two-step process. First, the cells need to be detached, induced by the cell culture flask’s rotation and the subsequent fluid flow, as well as the presence of air bubbles. Once the cells are detached and in suspension, random positioning prevents sedimentation, allowing 3D aggregates to form. In a comparative shear stress experiment using defined fluid flow paradigms, transcriptional responses were triggered comparable to exposure of FTC-133 cells to the RPM. In summary, the RPM serves as a simulator of microgravity by randomizing the impact of Earth’s gravity vector especially for suspension (i.e., detached) cells. Simultaneously, it simulates physiological shear forces on the adherent cell layer. The RPM thus offers a unique combination of environmental conditions for in vitro cancer research.

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“…Since the health conditions affect physiological systems in the human body, including the central nervous, cardiovascular, musculoskeletal, immune, and hepatic systems, the space flight could result in the disruption of circadian rhythms, increased risk of cancer, and genetic mutations. For instance, recently, space technology merging the 3D organoid technology has been applied to study early mutational events in human DNA due to spaceflight exposure ( Larose, 2020 ). Thus the development of effective counter-measures and health systems play a key role to explore the next phase of space exploration.…”

Section: Cancer Progression In the Space Environmentmentioning

confidence: 99%

Mechanobiological Implications of Cancer Progression in Space

Kim

Shin

Kim

2021

Front. Cell Dev. Biol.

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The human body is normally adapted to maintain homeostasis in a terrestrial environment. The novel conditions of a space environment introduce challenges that changes the cellular response to its surroundings. Such an alteration causes physical changes in the extracellular microenvironment, inducing the secretion of cytokines such as interleukin-6 (IL-6) and tumor growth factor-β (TGF-β) from cancer cells to enhance cancer malignancy. Cancer is one of the most prominent cell types to be affected by mechanical cues via active interaction with the tumor microenvironment. However, the mechanism by which cancer cells mechanotransduce in the space environment, as well as the influence of this process on human health, have not been fully elucidated. Due to the growing interest in space biology, this article reviews cancer cell responses to the representative conditions altered in space: microgravity, decompression, and irradiation. Interestingly, cytokine and gene expression that assist in tumor survival, invasive phenotypic transformation, and cancer cell proliferation are upregulated when exposed to both simulated and actual space conditions. The necessity of further research on space mechanobiology such as simulating more complex in vivo experiments or finding other mechanical cues that may be encountered during spaceflight are emphasized.

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Tumors in Space: Preparation for Spaceflight

Cited by 4 publications

References 20 publications

Proton and alpha radiation-induced mutational profiles in human cells

Proton and alpha radiation-induced mutational profiles in human cells

Fluid and Bubble Flow Detach Adherent Cancer Cells to Form Spheroids on a Random Positioning Machine

Mechanobiological Implications of Cancer Progression in Space

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