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 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.

Microgravity, Stem Cells, and Cancer: A New Hope for Cancer Treatment

“…Prasanth et al exposed erythroleukemic and leukemic cancer cells to microgravity with RCCS for a duration of 48 h. They discovered that when leukemic cancer cells were treated with daunorubicin, they showed increased chemotactic migration ( p < 0.01) following simulated microgravity (s- μg ) compared to the normal gravity on earth (1g). This suggests that microgravity affects the response of cancer cells to chemotherapy in a drug-dependent manner [ 43 ]. There are few publications regarding the effect of chemotherapeutic drugs in a microgravity environment, which is still an open discussion with many areas for improvement.…”

“…It has been found that resistance to chemotherapeutic drugs is reduced in tumor cell lines in microgravity environments, but this has been tested in a limited number of tumors and with only a few chemotherapeutics [ 43 ]. Currently, there are no studies in the literature examining the effect of radiotherapy in true and simulated microgravity environments.…”

Cancer Studies under Space Conditions: Finding Answers Abroad

“…Cells treated with doxorubicin showed enhanced migration both in 1 g and following μ g . The increase in ROS production in s-µ g was cell-type dependent, with acute myeloid leukaemia (AML) cells showing no increase, while chronic myeloid leukaemia (CML) cells have an increase in ROS production [ 146 ].…”

Breast Cancer Cells in Microgravity: New Aspects for Cancer Research

“…So far this was the first study investigating the influence of s-µg on the effects of breast cancer treatment. However, results from leukemic cells have already indicated that s-µg is able to modulate the cancer cell response to chemotherapy [103]. Authors proposed that (s-)µg can be a powerful additional treatment for cancer cells and an immunomodulatory tool for the development of new immunotherapies, offering to open up new horizons to novel strategies for breast cancer therapy [102,103].…”