Planar neural organoids as an advanced in vitro model to study patient-derived melanoma metastasis
摘要
Metastasis, which occurs when cancer cells spread from their original site in the body to other organs - is the leading cause of death in cancer patients. Conventional two-dimensional (2D) cell cultures along with orthotopic animal models are widely used to study and develop therapeutics for metastatic cancers. However, 2D cell cultures do not accurately reflect the physiology of real tissues, and the results obtained from the orthotopic animal models cannot always be applied to humans due to the interspecies differences. The recent emergence of human organoid models provides unique opportunities to study the complex cellular interactions in a near-physiological 3D environment. In this study, we have engineered an in vitro melanoma metastasis model using patient-derived melanoma cells and human-induced pluripotent stem cells (iPSCs)-derived planar neural organoids (PNOs). We investigated metastatic cancer processes such as the growth of melanoma cells, and evaluated the effects of anti-cancer drug treatment on it. Our results demonstrated that the 3D PNO system served as a more effective in vitro model than conventional 2D cultures to study melanoma brain metastases, and this PNO system can also be used to model other types of poorly understood metastatic cancers under physiological environments.