Interactions of natural killer cells and pancreatic cancer cells in simulated microgravity

Abstract

Abstract One of the major concerns of long-duration spaceflight is the exposure of astronauts to space radiation and the potential for cancer development. Natural killer (NK) cells continuously survey the body for such abnormalities and upon detection are activated to produce pro-inflammatory cytokines as well as cytotoxins which induce apoptosis of the cancer cells. This study employed the rotary cell culture system to generate a simulated microgravity (SMG) environment in order to assess its effect upon the growth of human cancer cells and their susceptibility to lysis by NK cells. We found that SMG diminishes the numbers of both pancreatic cancer cells and NK92MI, a human NK cell line, over a 7 d culture period. Additionally, SMG NK92MI cells had a ~50% decrease in cytotoxicity against PANC-1 pancreatic cancer cells. Surprisingly, a long-term SMG culture of up to 14 d resulted in complete restoration of NK92MI cell cytotoxic function. Interestingly, SMG cultured NK92MI cells produced more IFN-gamma than Static NK cells throughout the time periods assessed. In comparison, 7 d culture of pancreatic cancer cells in SMG led to a ~50% reduction in the ability of either Static or SMG NK92MI cells to induce apoptosis in the SMG cultured cancer cells. Therefore, over a two-week period in SMG culture, NK92MI cells were able to adapt to the environment and recover cytotoxic function, however, pancreatic cancer cells cultured in SMG acquired resistance to lysis by the NK cells. Hence, cancer cells developing in astronauts in microgravity might have a greater potential to resist NK cell control than in patients here on Earth which upon elucidation may aid in the identification of relevant new tumor targets for therapeutics.