Cancer Studies under Space Conditions: Finding Answers Abroad

Abstract

In this review article, we discuss the current state of knowledge in cancer research under real and simulated microgravity conditions and point out further research directions in this field. Outer space is an extremely hostile environment for human life, with radiation, microgravity, and vacuum posing significant hazards. Although the risk for cancer in astronauts is not clear, microgravity plays a thought-provoking role in the carcinogenesis of normal and cancer cells, causing such effects as multicellular spheroid formation, cytoskeleton rearrangement, alteration of gene expression and protein synthesis, and apoptosis. Furthermore, deleterious effects of radiation on cells seem to be accentuated under microgravity. Ground-based facilities have been used to study microgravity effects in addition to laborious experiments during parabolic flights or on space stations. Some potential 'gravisensors' have already been detected, and further identification of these mechanisms of mechanosensitivity could open up ways for therapeutic influence on cancer growth and apoptosis. These novel findings may help to find new effective cancer treatments and to provide health protection for humans on future long-term spaceflights and exploration of outer space.

Keywords: gene expression; gravisensors; gravitation; mechanobiology; neoplasms; radiation; review; weightlessness.

Figure 1

Factors involved in carcinogenesis and promotion of tumour growth.

Figure 2

Forces acting in the microgravity environment. A small diagram depicts the weightlessness effect over cells used in microgravity studies and which cells suffer in ISS or parabolic flight experiments: 1.- The mass of the cell exerts a force directly proportional to its mass and the Earth gravity and inversely proportional to its distance to the Earth. 2.- In microgravity conditions, for example in a parabolic flight experiment or inside the International Space Station, the reaction force exerted by the surface against which the subject stands disappears, so the cell is not feeling this physical input anymore. 3.- We call this “weightlessness”, a term that usually appears in microgravity research. Please be aware that other forces like the stiffness of the material’s surface of the flask should not be disregarded. “Dotted”arrow: Direction of the pull of gravity. Arrow with a red X: Direction of the reaction force exerted by the surface, which is lost in microgravity conditions. g: Acceleration of gravity.

Figure 3

Model for gravisensing in non-specialised mammalian cells: Model for stiffness sensing adapted to µg-studies in cell cultures; any disturbance in this mechanotransduction process will trick the cell into thinking that it is in a µg-environment or, what could be similarly interpreted, a soft ECM. Different mechanotransduction mechanisms presented: (1) Direct force transmission through focal adhesions to organelles, (2) The regulation of mechanoresponsive transcription factor complexes (we show only YAP/TAZ, but others like MTRF are also important). In addition, a vital mechanotransduction process occurs through mechanically gated ion channels, like Piezo1/2, which is related to the tension of the plasma membrane. Responses to soft ECM adapted from [58]. ECM: Extracellular Matrix; LATS: Large Tumour Suppressor; MLCK: Myosin light-chain kinase; MLCP: Myosin light-chain phosphatase; NMII: Non muscle myosin II; ROCK: Rho-associated protein kinase; SRC: Proto-oncogene tyrosine-protein kinase Src; YAP: yes-associated protein. Figure created in the Mind the Graph platform.

Figure 4

Summary of the effects of radiation on cells. DNA: Deoxyribonucleic acid (Adapted from [62]).

Figure 5

The effects of microgravity on cancer cells. FP: filopodia; LP: lamellipodia; ECM: extracellular matrix; VEGF: Vascular Endothelial Growth Factor. (The figure was originally published by our group in Nassef et al. [20]).