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

Abstract

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 1 /CD133 1 CTCs were identified in 65% of patients at baseline and 47.8% after systemic therapy (p 5 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 1 /CD133 1 CTCs. Before any treatment, CK 1 /CD133 1 CTCs were more frequently isolated in patients with luminal BC subtype. No statistically significant differences were found between proportion of CK 1 /CD133 1 CTCs and BC subtypes after systemic therapy, implying a relative enrichment of CK 1 /CD133 1 CTCs in triple negative and HER2-amplified tumors. While CK 1 /CTCs decreases after chemotherapy when analyzing the whole population, CK 1 / CD133 1 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.Breast cancer (BC) is a complex and heterogeneous disease comprising multiple tumor entities associated with distinctive different biological feature, clinical behaviors and response to therapy. The current classification of BC is based on the pattern of expression of the hormone receptors (HR) estrogen receptor and/or progesterone receptor, and human epidermal receptor 2 (Her2) that identify three major BC subtypes: luminal tumors, which are HR positive and Her2 negative; Her2 amplified tumors; and those tumors with lack of expression of the three receptors, referred to as triple negative (TN) BC. 1 Despite advances in BC treatments, primary and acquired resistance to cancer therapies remains a challenge especially in nonmetastatic patients. Cancer stem cells (CSC) have been

The Ribonucleic Complex HuR-MALAT1 Represses CD133 Expression and Suppresses Epithelial–Mesenchymal Transition in Breast Cancer

“…We showed that genetic downregulation of any components of the complex led to an upregulation of the CD133 gene, and to the following switch of the ER þ breast cancer cells to a more basal-like phenotype. Interestingly, CD133 is epigenetically regulated and highly expressed in basal-like TNBC (41,42), and is a concurring cause of the aggressiveness of this breast cancer subgroup (11,43). Importantly, we did not detect HuR, and its complex, on the two novel observations can be gathered.…”

Implications of Different Cancer Stem Cell Phenotypes in Breast Cancer

“…Moreover, CD133 was also proved to be suitable in the identification of CSCs in triplenegative breast cancers through several in vitro (68,69) and in vivo studies (70). In addition, the recent use of CD133 to detect circulating tumor cells in patients with triple-negative breast cancer (71,72) has increased the attention on this marker, emphasizing its role in prognosis in this breast cancer subtype. Expression of CD133 was also recently reported in 22 out of 25 cases of inflammatory breast cancer (13).…”

The Expressions of Cancer Stem Cell Markers and Nonclassical HLA antigens in Breast Tumors

“…Stage IIIB: the tumor has grown into the chest wall or skin (T4), and one of the following applies: It has not spread to the lymph nodes (N0), It has spread to 1 to 3 axillary lymph nodes and/or tiny amounts of cancer are found in internal mammary lymph nodes on sentinel lymph node biopsy (N1), It has spread to 4 to 9 axillary lymph nodes, or it has enlarged the internal mammary lymph nodes (N2), The cancer hasn't spread to distant sites (M0) CD133 can also be detected in healthy cells like hematopoietic stem cells and neuronal and glial stem cells (6), so the main function of CD133 in tumor progression remains unknown. Contrary to CD44, it has been shown that CD133 is associated with tumor angiogenesis, metastasis, and poor prognosis in malignant BC patients (33)(34)(35). We found significantly increased expression of both CD44 and CD133 in the advanced-stage BC tissue compared with non-cancer breast biopsy tissues.…”