Abstract
Microgravity or the condition of apparent weightlessness causes bone, muscular and immune system dysfunctions in astronauts following spaceflights. These organ and system-level dysfunctions correlate with changes induced at the single cell level both by simulated microgravity on earth as well as microgravity conditions in outer space (as in the international space station). Reported changes in single bone cells, muscle cells and white blood cells include structural/morphological abnormalities, changes in gene expression, protein expression, metabolic pathways and signaling pathways, suggesting that cells mount some response or adjustment to microgravity. However, the implications of such adjustments on many cellular functions and responses are not clear largely because the primary mechanism of gravity sensing in animal cells is unknown. Here, we used a rotary cell culture system developed by NASA to subject leukemic and erythroleukemic cancer cells to microgravity for 48 h and then quantified their innate immune response to common anti-cancer drugs using biophysical parameters and our recently developed quantum-dot-based fluorescence spectroscopy. We found that leukemic cancer cells treated with daunorubicin show increased chemotactic migration (p < 0.01) following simulated microgravity (µg) compared to normal gravity on earth (1 g). However, cells treated with doxorubicin showed enhanced migration both in 1 g and following µg. Our results show that microgravity modulates cancer cell response to chemotherapy in a drug-dependent manner. These results suggest using simulated microgravity as an immunomodulatory tool for the development of new immunotherapies for both space and terrestrial medicine.
Highlights
Physical forces including electromagnetism and gravity have shaped the evolution of life on earth and continue to influence living processes in organisms
With microgravity producing differences in reactive oxygen species (ROS) generation between a model of acute myeloid leukemia (AML), that is, HL60, and a model of chronic myelogenous leukemia (CML), that is, K562, which we have shown in this work, our suggested use of microgravity as an immunomodulatory tool for drug development becomes even more compelling
Beginning with the hypothesis that microgravity might alter the effects of cancer drugs on cellular functions involved in metastasis, such as migration, we have shown in this work that post-microgravity anticancer treatment can lead to results that are different from those of in vitro anticancer treatment administered in normal gravity (1 g)
Summary
Physical forces including electromagnetism and gravity have shaped the evolution of life on earth and continue to influence living processes in organisms. Changes in such forces produce profound biological effects. Microgravity in outer space and simulated microgravity on earth cause changes in biological cells, tissues and organs. In order to enhance space exploration, NASA and other space programs have developed several spaceflight analogue systems on earth, including unique suspension cell culture systems such as the rotary cell culture system, RCCS [1]. It turns out that such analogue systems lead to discoveries and inventions with potential use for enhancing terrestrial life, medicine and further research. Cancer research has employed microgravity as a condition for studying
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