Translational models of 3-D organoids and cancer stem cells in gastric cancer research

Abstract

It is postulated as a general concept of cancer stem cells (CSCs) that they can produce cancer cells overtly and repopulate cancer progenitor cells indefinitely. The CSC niche is part of a specialized cancer microenvironment that is important to keep the phenotypes of CSCs. Stem cell- and induced pluripotent stem cell (iPSC)-derived organoids with genetic manipulation are beneficial to the investigation of the regulation of the microenvironment of CSCs. It would be useful to assess the efficiency of the cancer microenvironment on initiation and progression of cancers. To identify CSCs in cancer tissues, normal cell organoids and gastric cancer organoids from the cancerous areas, as well as iPSCs, were established several years ago. However, many questions remain about the extent to which these cultures recapitulate the development of the gastrointestinal tract and the mechanism of Helicobacter pylori-induced cancer progression. To clarify the fidelity of human organoid models, we have noted several key issues for the cultivation of, and differences between, normal and cancerous organoids. We developed precise culture conditions for gastric organoids in vitro to improve the accuracy of the generation of organoid models for therapeutic and medical applications. In addition, the current knowledge on gastrointestinal CSC research, including the topic of CSC markers, cancer cell reprogramming, and application to target cancer cell plasticity through niches, should be reinforced. We discuss the progression of cancers derived from human gastric organoids and the identification of CSCs.