A comparative study of metastatic potentials of three different cancer stem cell models

Metastasis is one of the major causes of cancer deaths. However, the mechanisms of cancer cells acquiring aggressiveness and metastatic potential are still under investigation. Although cancer stem cells (CSCs) have been suggested as tumor initiating cells responsible for cancer metastasis, no sufficiently practical models have been found because of less availability of CSCs. We have developed novel CSC models derived from mouse induced pluripotent stem cells (miPSCs) in the presence of conditioned media (CM) from different cancer cell lines. Here, we tried to establish the models of metastasis using three different CSC models, miPS-LLCev, miPS-BT549cm and miPS-Huh7cm cells. The metastatic abilities of these CSC models were evaluated by intraperitoneal injections into mice. The developed metastases were histologically analyzed and the differences in gene expression between parental and metastasized cells were assessed. The expression of CSC and stemness markers was maintained in the cells isolated from metastasis. The three types of CSCs were further analyzed by RNA-sequencing to identify the enriched cytoplasmic signaling pathways. As a result, the three CSC models exhibited different patterns of metastases while the metastasis of miPS-LLCev cells appeared the most aggressive demonstrating hepatocellular carcinoma, which developed from the inside of the liver, as well as pulmonary metastasis. Metastasis related “HIF-1 pathway” was nominated as the candidate of enriched pathway in miPS-LLCev and miPS-Huh7cm cells implying that these CSC models possessed distinguished metastatic potential. Therefore, we concluded that the CSC models developed in this study would provide good models of metastasis linked with the aggressiveness.