Mechanobiological Implications of Cancer Progression in Space

Abstract

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.

Microgravity Modifies the Phenotype of Fibroblast and Promotes Remodeling of the Fibroblast–Keratinocyte Interaction in a 3D Co-Culture Model

“…According to non-equilibrium thermodynamics that govern dissipative processes, these can display unexpected behaviors, such as cytoskeleton arrangement, cell division, and mechanotransduction of physical stresses, to name a few [25,26]. Specifically, dynamic adhesion processes between cells and their microenvironment are profoundly affected in µ G, leading to bewildering modification in cellular aggregation and tissue architecture [27,28].…”

MRTF may be the missing link in a multiscale mechanobiology approach toward macrophage dysfunction in space

“…*Parabolic Flight, †Simulated microgravity culture vessel (not flight), ‡Long-term orbital spaceflight. et al, 2018), cancer progression (Kim et al, 2021), circadian rhythm disruption (Simmet et al, 2013), and accelerated atherosclerosis (Meerman et al, 2021). For example, bloodcirculating monocytes are recruited as pro-inflammatory Mϕ toward atherosclerotic lesions because of many factors including radiation (Patel, 2020), reactive oxygen species (ROS) (Wang Y. et al, 2014), adhesion proteins (Yang et al, 2005), and motility (Mukherjee et al, 2022)-all of which are afflicted by spaceflight.…”

“…These factors are space- and time-dependent, and thus differential changes observed across experimental timescales were often interpreted as an adaptation to microgravity ( Meloni et al, 2006 ; Paulsen et al, 2015 ; Ludtka et al, 2021b ). Instead of such broad interpretations, however, mechanistic understandings are necessary for safe, effective treatment of spaceflight diseases such as immune dysregulation ( Crucian et al, 2018 ), cancer progression ( Kim et al, 2021 ), circadian rhythm disruption ( Simmet et al, 2013 ), and accelerated atherosclerosis ( Meerman et al, 2021 ). For example, blood-circulating monocytes are recruited as pro-inflammatory Mϕ toward atherosclerotic lesions because of many factors including radiation ( Patel, 2020 ), reactive oxygen species (ROS) ( Wang Y. et al, 2014 ), adhesion proteins ( Yang et al, 2005 ), and motility ( Mukherjee et al, 2022 )—all of which are afflicted by spaceflight.…”

MRTF May Be the Missing Link in a Multiscale Mechanobiology Approach toward Macrophage Dysfunction in Space

“…These factors are space-and time-dependent, and thus differential changes observed across experimental timescales were often interpreted as an adaptation to microgravity (Meloni et al, 2006;Paulsen et al, 2015;Ludtka and Silberman et al, 2021). Instead of such broad interpretations, however, mechanistic understandings are necessary for safe, effective treatment of spaceflight diseases such as immune dysregulation (Crucian et al, 2018), cancer progression (Kim et al, 2021), circadian rhythm disruption (Simmet, 2013), and accelerated atherosclerosis (Meerman et al, 2021). For example, blood-circulating monocytes are recruited as pro-inflammatory Mφ toward atherosclerotic lesions because of many factors including radiation (Patel, 2020), reactive oxygen species (ROS) (Y. , adhesion proteins (Yang et al, 2005), and motility (Mukherjee et al, 2022) space.…”