Microgravity modulates effects of chemotherapeutic drugs on cancer cell migration

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 hours and then quantified their innate immune-response to common anti-cancer drugs using biophysical parameters and our recently developed quantum-dots-based fluorescence spectroscopy. We found that leukemic cancer cells treated with daunorubicin show increased chemotactic migration (p < 0.01) following simulated microgravity (g) compared to normal gravity on earth (1g). However, cells treated with doxorubicin showed enhanced migration both in 1g and following g. 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.