Using a spaceflight three-dimensional microenvironment to probe cancer-stromal interactions

Abstract

The effects of microgravity and spaceflight on cancer development and progression have not been defined. We provide an introductory review of our studies of microgravity and spaceflight on human prostate cancer cell growth, with emphasis on the investigation of cancer-stromal interaction under 3-dimensional (3-D) rotary wall vessel (RWV) bioreactor and space flight conditions. We used several 3-D co-culture models to mimic the in situ situation of tumor growth, which depends on constant interaction with resident mesenchymal stromal cells of the tumor microenvironment. Through co-culturing prostate cancer cells with mesenchymal stromal cells in 3-D in the RWV, we found 3-D cancer-stromal interaction facilitating cancer cells to acquire permanent and irreversible genotypic and phenotypic alterations. We further determined that under 3-D co-culture conditions, metastasis-initiating cells (MICs) could recruit and reprogram non-tumorigenic or bystander cells of the tumor microenvironment to mimic MICs. In a study in spaceflight, we found that cancer-stromal co-culture in 3-D in the RWV resulted in markedly accelerated cell proliferation. Mechanistically, the tropism of 3-D culture in the RWV or microgravity on cancer growth and progression appeared to be mediated by increased communications between cancer and the interacting stromal cells via soluble and insoluble factors, although additional mechanisms may also be contributory. These factors should be further investigated as targets for inhibiting tumor growth and cancer progression.