CD133 expression in circulating tumor cells from breast cancer patients: Potential role in resistance to chemotherapy

CD133 has been associated with cell properties such as self renewal, migration and vasculogenic mimicry, potentially involved in generation of circulating tumor cells (CTCs). We characterized CD133 expression in CTCs of 98 nometastatic breast cancer (BC) patients. CTCs were isolated by immunomagnetic techniques using magnetic beads labeled with a multicytokeratin(CK)-specific antibody (CK3-11D5) and CTCs and CD133 detection through immunocytochemical methods. CK+/CD133(+) CTCs were identified in 65% of patients at baseline and 47.8% after systemic therapy (p = 0.53). Correlation of CD133 status in CTCs with classical clinicopathological characteristics and response to therapy was performed. Her2 not amplified and low Ki-67 index were positively correlated with presence of CK+/CD133(+) CTCs. Before any treatment, CK+/CD133(+) CTCs were more frequently isolated in patients with luminal BC subtype. No statistically significant differences were found between proportion of CK+/CD133(+) CTCs and BC subtypes after systemic therapy, implying a relative enrichment of CK+/CD133(+) CTCs in triple negative and HER2-amplified tumors. While CK+/CTCs decreases after chemotherapy when analyzing the whole population, CK+/CD133(+) CTCs were enriched in post-treatment samples in nonluminal BC subtypes. These findings suggest the potential role of CD133 as a promising marker of chemoresistance in nonluminal BC patients. Further prospective studies and extensive preclinical modeling will be needed to confirm whether CD133 is a marker of resistance to chemotherapy, and its role as a target for novel anticancer therapies targeting cancer stem cells and tumor vasculature. What's new? Despite advances in breast cancer treatments, primary and acquired resistance to cancer therapies remains a challenge. Here the authors looked at the expression of CD133a glycoprotein associated with stem cell and migratory properties and vasculogenic mimicryin circulating tumor cells (CTCs) of non-metastatic patients. CD133 was widely expressed, particularly in patients with luminal tumors before they received treatment. A relative enrichment was detected in non-luminal tumor subtypes following systemic therapy, suggesting a potential role of CD133+ CTCs in chemoresistance. Characterization of CD133 in CTCs might help to develop new therapeutic approaches targeting cancer stem cells and tumor vasculature.