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

Abstract

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.

Role of KDM2B epigenetic factor in regulating calcium signaling in prostate cancer cells

“…More specifically, gene and protein expression of both markers was markedly reduced in DU-145 with KDM2B overexpression ( Zacharopoulou et al, 2018a ). We have also shown that EMT phenotypes are upregulated in CTCs, promoting their migration into the bloodstream ( Kallergi et al, 2011 , Pantazaka et al, 2021 , Vardas et al, 2022 ). KDM2B is involved in various signaling pathways crucial in tumorigenesis ( Yan et al, 2018 ).…”

HMGB2 upregulation promotes the progression of hepatocellular carcinoma cells through the activation of ZEB1/vimentin axis

“…Proteomics related research reported that vimentin is a metastasis related factor of various malignant tumors, such as prostate cancer and breast cancer, which indicates that it may play an important role in tumor progression and become a potential biomarker of metastasis ( 31 ). ZEB1, a master regulator of the EMT, which regulates the expression of vimentin ( 32 ), has been reported to facilitate tumor invasion and metastasis by inducing EMT in various tumors. ZEB1 belongs to the E-box binding zinc finger protein family and promotes downstream gene transcription by binding to E-box promoter elements ( 33 ).…”

Significance of circulating tumor cells in lung cancer: a narrative review

“…Intravasation of CTCs via EMT after active crossing of tumor stroma is expected to result in fully viable and not apoptotic cells. Marker-independent CTC enrichment techniques demonstrate a variety of CTC EMT partial phenotypes with minor upregulation in vimentin and downregulation in E-cadherin without a true cell-type transformation ( 82 , 83 ). Furthermore, the number of CTCs that have intravasated seems to be correlated to the microvessel density of the tumor but not to the tumor mass.…”