The Significance of Epithelial-to-Mesenchymal Transition for Circulating Tumor Cells

Abstract

Epithelial to mesenchymal transition (EMT) is a process involved in embryonic development, but it also plays a role in remote metastasis formation in tumor diseases. During this process cells lose their epithelial features and adopt characteristics of mesenchymal cells. Thereby single tumor cells, which dissolve from the primary tumor, are enabled to invade the blood vessels and travel throughout the body as so called “circulating tumor cells” (CTCs). After leaving the blood stream the reverse process of EMT, the mesenchymal to epithelial transition (MET) helps the cells to seed in different tissues, thereby generating the bud of metastasis formation. As metastasis is the main reason for tumor-associated death, CTCs and the EMT process are in the focus of research in recent years. This review summarizes what was already found out about the molecular mechanisms driving EMT, the consequences of EMT for tumor cell detection, and suitable markers for the detection of CTCs which underwent EMT. The research work done in this field could open new roads towards combating cancer.

Detection of AXL expression in circulating tumor cells of lung cancer patients using an automated microcavity array system

“…Other potential markers such as CD133, one of the cancer stem cell markers have been employed for mesenchymal‐like CTCs isolation methods . There are many reports indicating that CTCs expressing high levels of EMT markers in several cancer types such as breast, prostate, and colorectal, are often accompanied by the expression of cancer stem cell markers, suggesting the utility of incorporating stem cell markers such as CD133 . However, the relationship between EMT markers and CD133 on CTCs in lung cancer is not well‐understood.…”

“…40 There are many reports indicating that CTCs expressing high levels of EMT markers in several cancer types such as breast, prostate, and colorectal, are often accompanied by the expression of cancer stem cell markers, suggesting the utility of incorporating stem cell markers such as CD133. [47][48][49] However, the relationship between EMT markers and CD133 on CTCs in lung cancer is not well-understood. Potential of other EMT markers including CD133 to detect mesenchymal-like CTCs should be pursued in the future, nonetheless.…”

Prognostic significance of PD‐L1 expression on cell‐surface vimentin‐positive circulating tumor cells in gastric cancer patients

“…Increasing evidence has demonstrated that the cellular process in which epithelial cells acquire a mesenchymal phenotype (epithelial–mesenchymal transition, EMT) leads to an increase in cellular invasion and spread (Diepenbruck and Christofori, ; Dongre and Weinberg, ). Such EMT–CTC subpopulations are considered the roots of metastases (Kölbl et al , ). Currently, selecting specific markers for the detection of EMT–CTCs is an enormous challenge facing those in the CTC technology field (Yahyazadeh Mashhadi et al , ).…”

Epithelial–mesenchymal plasticity and circulating tumor cells: Travel companions to metastases

“…involves sequential EMTs followed by mesenchymal-epithelial transitions (METs) at different body locations (Tsai and Yang, 2013;Jolly et al, 2015a;Liu et al, 2015;Beerling et al, 2016;Celia-Terrassa and Kang, 2016;Chaffer et al, 2016;Diepenbruck and Christofori, 2016;Kolbl et al, 2016). Thus, a switch toward a more mesenchymal state (EMT) is considered to contribute to the first phases of the metastatic translocation, i.e., tumor invasion, intravasation, liberation of CTCs and survival in the bloodstream, and metastatic niche formation.…”

“…EMT has indeed rapidly emerged as a process endowing tumor cells with properties that may functionally impact CTC life cycle (Bonnomet et al, 2010;Barriere et al, 2014;Krawczyk et al, 2014;Aceto et al, 2015;Jolly et al, 2015a;Liu et al, 2015;McInnes et al, 2015;Pantel and Speicher, 2015;Kolbl et al, 2016;Alix-Panabieres et al, 2017), including invasive/motile properties (Nieto et al, 2016), resistance to apoptosis/anoikis (Tiwari et al, 2012;Frisch et al, 2013;Cao et al, 2016), and stemness properties (Ombrato and Malanchi, 2014;Ye and Weinberg, 2015;Fabregat et al, 2016). EMT has indeed rapidly emerged as a process endowing tumor cells with properties that may functionally impact CTC life cycle (Bonnomet et al, 2010;Barriere et al, 2014;Krawczyk et al, 2014;Aceto et al, 2015;Jolly et al, 2015a;Liu et al, 2015;McInnes et al, 2015;Pantel and Speicher, 2015;Kolbl et al, 2016;Alix-Panabieres et al, 2017), including invasive/motile properties (Nieto et al, 2016), resistance to apoptosis/anoikis (Tiwari et al, 2012;Frisch et al, 2013;Cao et al, 2016), and stemness properties (Ombrato and Malanchi, 2014;Ye and Weinberg, 2015;Fabregat et al, 2016).…”