Mesenchymal and stemness circulating tumor cells in early breast cancer diagnosis

Abstract

BackgroundEpithelial mesenchymal transition (EMT) is a crucial event likely involved in dissemination of epithelial cancer cells. This process enables them to acquire migratory/invasive properties, contributing to tumor and metastatic spread. To know if this event is an early one in breast cancer, we developed a clinical trial. The aim of this protocol was to detect circulating tumor cells endowed with mesenchymal and/or stemness characteristics, at the time of initial diagnosis. Breast cancer patients (n = 61), without visceral or bone metastasis were enrolled and analysis of these dedifferentiated circulating tumor cells (ddCTC) was realized.MethodsAdnaGen method was used for enrichment cell selection. Then, ddCTC were characterized by RT-PCR study of the following genes: PI3Kα, Akt-2, Twist1 (EMT markers) and ALDH1, Bmi1 and CD44 (stemness indicators).ResultsAmong the studied primary breast cancer cohort, presence of ddCTC was detected in 39% of cases. This positivity is independant from tumor clinicopathological factors apart from the lymph node status.ConclusionsOur data uniquely demonstrated that in vivo EMT occurs in the primary tumors and is associated with an enhanced ability of tumor cells to intravasate in the early phase of cancer disease. These results suggest that analysis of circulating tumor cells focused on cells showing mesenchymal or stemness characteristics might facilitate assessment of new drugs in clinical trials.

Implications of Mesenchymal Cells in Cancer Stem Cell Populations: Relevance to EMT

“…In metastatic breast cancer patients, a major proportion of CTCs were found to display EMT and tumor stem cell properties (19). This study was further extended to CTCs from breast cancer patients without diagnosis of metastasis, suggesting that acquisition of EMT and stemness can occur early in the dissemination process similar to that observed in pancreatic cancer (9,20,21). These studies have been significantly extended by a recent study from Yu et al showing that CTCs from metastatic breast cancer exhibit features of EMT (Figure 2) (22).…”

Pooled Analysis of the Prognostic Relevance of Circulating Tumor Cells in Primary Breast Cancer

“…One potential problem with the use of epithelial-specific markers is that more aggressive CTC types are likely to undergo phenotypic changes associated with the epithelial-to-mesenchymal transition (EMT). In cancer cells, EMT is considered a crucial event for metastatic spreading, because it facilitates primary tumor dissemination into the blood stream as well as migration and invasion into secondary metastatic sites (1,31,32). During EMT, cells exhibit reduced levels of cell-cell adhesion and increased mesenchymal protein expression, which is accompanied by a corresponding loss of epithelial marker expression (33).…”

The role of epithelial plasticity in prostate cancer dissemination and treatment resistance

“…Importantly, many CTCs have a dual epithelial and mesenchymal/stemness phenotype, suggesting the importance of this duality in treatment resistance and dissemination [15]. This EP biology is not unique to PC, as variable phenotypes have been observed in CTCs from other malignancies, such as lung [211, 212], colorectal [213], and breast cancer [214], suggesting a broad conceptual parallel. Therefore, EP may explain the underdetection of CTCs in patients with advanced malignancy using the standard epithelial antigen-based technology [15, 215, 216].…”