Human cancers, such as breast and colon cancers, contain cancer stem cells (CSCs) which are involved in various aspects of tumor progression, such as recurrence, metastasis, and drug resistance. The fact that metastases can appear years or even decades after the surgical removal of the primary tumor strongly suggests a critical role of metastatic CSCs (mCSCs) in cancer progression.
miRNAs are short non-coding RNAs that regulate various cellular processes, such as differentiation, proliferation, apoptosis, and stem cell maintenance. We have previously reported that miRNAs, such as miR-200c, miR-183, and miR-142, are differentially expressed between human breast CSCs and other non-tumorigenic cancer cells. Both miR-200c and miR-183 suppress the expression of a self-renewal gene BMI1. miR-142 targets APC and activates the WNT signaling pathway that is implicated in stem cell maintenance.
Then, we established the PDX models of human breast cancers and compared miRNA expression between CSCs at the primary site (pCSCs) and mCSCs. Although both pCSCs and mCSCs were within a CD44+/CD24-/low population, the expression profile of miRNAs was different between pCSCs and mCSCs. In addition, miRNAs that were downregulated in mCSCs than in pCSCs had potential to suppress the canonical WNT signaling activity, suggesting that the enhancement of WNT signaling activities is important to maintain mCSCs at the metastatic site.
Because mCSCs in metastatic regions are more resistant to cancer therapy, clarifying the molecular regulation of the human breast mCSCs will further advance our understanding of the roles of human breast CSCs in tumor progression and therapeutic resistance.
