scholarly journals Epithelial-to-mesenchymal transition of tumor cells: cancer progression and metastasis

2021 ◽  
Author(s):  
Vasileios Vardas ◽  
Eleni Politaki ◽  
Evangelia Pantazaka ◽  
Vassilis Georgoulias ◽  
Galatea Kallergi
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Cancer Progression ◽  
Epithelial To Mesenchymal Transition ◽  
Metastatic Breast ◽  
Cellsearch System ◽  
Mesenchymal Transition ◽  
Specificity And Sensitivity

Detection and characterization of circulating tumor cells (CTCs) with an epithelial-to-mesenchymal transition (EMT) phenotype is very important as it can contribute to the identification of high-risk for relapse and death patients. However, most of the methods are underestimating CTC numbers, due to their dependence on epithelial markers. In the current study, we evaluated the EMT phenotype in CTCs isolated from breast cancer (BC) patients, using the CellSearch system. Spiking experiments for the evaluation of the specificity and sensitivity of our method were performed using HeLa cells. Sixty-five breast cancer (BC) patients (47 early and 18 metastatic) were enrolled in the study. Vimentin is a mesenchymal marker which indicates tumoral cells acquiring invasive and malignant properties. We studied the vimentin (VIM) expression using the extra channel of the CellSearch system and an anti-vimentin antibody conjugated with FITC. In our present results, we reported the percentage of circulating tumor cells that expressed vimentin in early and in metastatic breast cancer patients. Interestingly, the incidence of cells with a CK-VIM+CD45- phenotype was detected in both settings. These cells were detected in 31.4% of CK-negative (11/35) and 82.3% of CK-positive (10/12) early BC patients. The corresponding numbers for metastatic disease were 15.4% (2/13) and 100% (5/5), respectively. Our results suggest that in CTC-negative patients, potentially undetectable tumor cells could be identified using the FDA-approved CellSearch system, based on the (CK-VIM+CD45-)-phenotype, offering additional information regarding the metastatic dissemination in cancer patients. Further experiments evaluating more biomarkers are necessary to elucidate the mechanisms that regulate tumorigenesis and metastasis.

scholarly journals The Role of Circulating Tumor Cells in Chemoresistant Metastatic Breast Cancer

2021 ◽  
Vol 10 (4) ◽  
pp. 684
Author(s):  
Lorena Alexandra Lisencu ◽  
Eduard-Alexandru Bonci ◽  
Alexandru Irimie ◽  
Ovidiu Balacescu ◽  
Cosmin Lisencu
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Disease Progression ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Metastatic Breast ◽  
Cochrane Library ◽  
Mesenchymal Transition

Breast cancer is the most frequent form of cancer among women and is one of the leading causes of death. Two routes of the metastatic process have been described: linear and parallel progression. A key factor is represented by circulating tumor cells (CTCs). CTCs detach from the primary tumor or develop from cancer stem cells (CSCs) that undergo epithelial-to-mesenchymal transition (EMT). CTCs migrate to the distant site where the reverse process occurs and a new tumor arises. One of the key problems of metastatic disease is chemoresistance, which leads to treatment failure and, eventually, death. The aim of this review is to present up-to-date data regarding the role of CTCs in chemoresistance in metastatic breast cancer (MBC) patients. A search in Cochrane Library and MEDLINE databases was performed. A total of 125 articles were identified. The results of the final 12 eligible studies revealed that CTCs having stem cell features and those with mesenchymal features are aggressive subtypes of cells that survive chemotherapy, being responsible for chemoresistance and thus for disease progression in MBC patients. The hemodynamic shear stress, alongside dynamic changes among CTCs during the disease, is also an important disease progression factor.

scholarly journals Fine analysis of atypical circulating tumor cells in metastatic breast cancer patients reveals subsets with different prognostic values

2020 ◽  
Author(s):  
Alexia Lopresti ◽  
Laurys Boudin ◽  
Pascal Finetti ◽  
Séverine Garnier ◽  
Anaïs Aulas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Mesenchymal Transition ◽  
Circulating Cells

Purpose: Circulating tumor cells (CTCs) have a tremendous potential for diagnosis and treatment of breast cancer patients. Here, we performed a unique analysis of all atypical circulating cells isolated with a filtration-based technology from metastatic breast cancer (mBC) patients. Patients and methods: The PERMED-01 study enrolled patients with mBC, refractory to systemic therapy, and with an accessible lesion to biopsy. We analyzed atypical circulating cells isolated from patients' blood at the time of inclusion using Screencell® Cyto device. For 23 out of 91 analyzed patients, this was completed by advanced immunofluorescence staining of atypical circulating cells. Subsets cut-offs were established using a two-component Gaussian finite Mixture Model, and evaluated for correlation with clinico-pathological data, including progression-free survival (PFS) and overall survival (OS). Results: Three subsets of atypical circulating cells, absent from controls (n=7), were observed in cancer patients (n=91): isolated (iCTCs), Clusters (CTM), and Giant CTCs (gCTCs). CTCs' median number was 8.33 per mL. Co-expression of stem and drug resistance markers was associated with intermediate epithelial to mesenchymal transition phenotype in CTM and gCTCs, but not in iCTCs. Presence of gCTC was associated with shorter PFS and OS. Concerning PFS, assigning an immunofluorescence-based Epithelial to Mesenchymal status improved their prognostic value. Conclusion: This study brings to light the diversity of CTCs in mBC patients and their specific molecular profiles regarding epithelial to mesenchymal transition, stemness and drug resistance status. It also highlights the involvement of an atypical circulating cell subset, the gCTCs, as a prognostic factor for PFS and OS.

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