Analysis of the hormone receptor status of circulating tumor cell subpopulations based on epithelial-mesenchymal transition: a proof-of-principle study on the heterogeneity of circulating tumor cells

Abstract

Although the enumeration of circulating tumor cells (CTCs) has been demonstrated to be a prognostic indicator in metastatic breast cancer, the heterogeneous characteristics of CTCs, such as variations in the epithelial-mesenchymal transition (EMT), may limit its broad clinical application. To investigate an uncomplicated and practicable detection approach based on the potential utility of the heterogeneity of CTCs from the standpoint of the EMT phenotype and ER/PR status of CTCs, an analysis was conducted using peripheral blood samples obtained from 28 metastatic breast cancer patients. The CanPatrol CTC enrichment technique was used to identify different CTC subpopulations, including epithelial-dominated CTCs, biophenotypic epithelial/mesenchymal CTCs, and mesenchymal-dominated CTCs, according to epithelial and mesenchymal markers. Furthermore, the hormone receptor (HR) status of each CTC was determined based on the expression levels of three reference genes and was characterized by four levels, which ranged from high-level expression to non-expression. We subsequently concluded that based on EMT phenotypes, the order of different CTC subgroups differed according to the HR expression status of the primary tumor. With respect to the HR status between tissues and CTCs, the variation tendency from high-level expression to non-expression of HR in CTCs was significantly correlated with the HR status of the primary tumor. The findings could provide evidence for the potential application of this uncomplicated and practicable detection approach for prognostic analysis and individualized endocrine therapeutic direction in a real-time manner via confirmation in further large-scale trials.

Phenotypes of circulating tumour cells predict time to castration resistance in metastatic castration‐sensitive prostate cancer

“…In the present study, we used the CanPatrol technique to count and characterize CTCs in a single test . The CanPatrol technique characterizes and classifies CTCs into epithelial, biophenotypic and mesenchymal phenotypes .…”

“…In the present study, we used the CanPatrol technique to count and characterize CTCs in a single test . The CanPatrol technique characterizes and classifies CTCs into epithelial, biophenotypic and mesenchymal phenotypes . Compared with the CellSearch platform, which uses anti‐EpCAM‐coated magnetic beads to capture CTCs, the CanPatrol technique uses an unbiased CTC isolation method that allows the isolation of CTCs that do not detectably express epithelial markers .…”

“…The CanPatrol technique characterizes and classifies CTCs into epithelial, biophenotypic and mesenchymal phenotypes [10][11][12][13][14][15][16]. Compared with the CellSearch platform, which uses anti-EpCAM-coated magnetic beads to capture CTCs, the CanPatrol technique uses an unbiased CTC isolation method that allows the isolation of CTCs that do not detectably express epithelial markers [10][11][12][13][14][15][16]. For example, the CanPatrol technique was used to detect CTCs in patients with nasopharyngeal, breast, liver, gastric, colorectal and nonsmall-cell lung cancer, and three phenotypes of CTCs are present in all [10][11][12][13][14][15][16].…”

“…Counting and characterization of CTCs were performed using the CanPatrol CTC technique (SurExam, Guangzhou, China), as described in detail in previous studies [10][11][12][13][14][15][16]. Specifically, the CanPatrol CTC technique employs a filtration system comprising a filtration tube containing a calibrated membrane (8-lm-diameter pores; SurExam), a manifold vacuum plate with valve settings (SurExam), an E-Z 96 vacuum manifold (Omega, Norcross, GA, USA), and a vacuum pump (Auto Science, Tianjin, China).…”

The Landscape of Circulating Tumor Cell Research in the Context of Epithelial-Mesenchymal Transition

“…Heterogeneous or lack of expression of ER in CTCs of patients with ER+ primary tumor was linked with resistance to fulvestrant of BC patients [159] . Interestingly, downregulation of ER is associated with acquiring a mesenchymal phenotype of BC cells due to EMT [160][161][162] . One of the ER isoforms, ERα36, which might be expressed in ERnegative BC (lacking the classical ERα isoform of 66 kDa molecular mass) [163] was identified as being linked with the EMT phenotype of BC cells [164] .…”