Exogenous Ribosome Incorporation Induces Lineage Transdifferentiation in Intestinal and Liver Cancer Cells

It has previously been shown that exogenous bacterial ribosomes added to somatic cells and various cancer cell lines generate ribosome-induced cell clusters (RICs) capable of transdifferentiating into multiple cellular lineages. However, the scope of ribosome-induced transdifferentiation in cancer cells remains poorly understood. This study aimed to analyze the effects of exogenous ribosome incorporation on human cancer cell lines, specifically the intestinal epithelial cell line Caco-2 and the hepatocellular carcinoma cell line HepG2. Caco-2 and HepG2 cells were cultured with purified bacterial ribosomes in human ES/iPS cell medium after trypsinization, resulting in the formation of ribosome-induced Caco-2 (RICs-Ca) and HepG2 (RICs-He) clusters, respectively. Both cell types exhibited alkaline phosphatase (AP) expression and the potential to transdifferentiate into adipocytes, chondrocytes, and osteoblasts, suggesting a more plastic cellular state. Our results support the idea that exogenous ribosome incorporation enhances the plasticity of cancer cells, promoting a multipotent-like cellular state and facilitating lineage transdifferentiation. This study further supports the role of ribosomes in modulating cell fate. Our findings present a novel approach to cancer cell lineage conversion with broader implications for regenerative medicine and cancer biology.