Implications of microgravity-induced cell signaling alterations upon cancer cell growth, invasiveness, metastatic potential, and control by host immunity

The human endeavor to venture beyond the orbit of Earth is challenged by both continuous space radiation and microgravity-induced immune dysfunction. If cancers were to develop in astronauts, it is unclear how these abnormal cells would grow and progress in the microgravity environment. It is unknown if the astronaut's immune response would be able to control or eradicate cancer. A better molecular understanding of how the mechanical force of gravity affects the cell as well as the aggressiveness of cancers and the functionality of host immunity is needed. This review will summarize findings related to microgravity-mediated alterations in the cell cytoskeleton, cell-cell, and cell-extracellular matrix interactions including cadherins, immunoglobulin superfamily of adhesion molecules, selectins, and integrins and related cell signaling. The effects of spaceflight and simulated microgravity on cell viability, cancer cell growth, invasiveness, angiogenesis, metastasis as well as immune cell functions and the subsequent signaling pathways involved will be discussed. Microgravity-induced alterations in function and signaling of the major anti-cancer immune populations will be examined including natural killer cells, dendritic cells, CD4⁺ T cells, and CD8⁺ T cells. Further studies regarding the molecular events impacted by microgravity in both cancer and immune cells will greatly increase the development of therapies to restrict tumor growth and enhance cancer-specific responses for both astronauts and patients on Earth.