Breast cancer circulating tumor cells with mesenchymal features—an unreachable target?

Abstract

Circulating tumor cells (CTCs) mediate dissemination of solid tumors and can be an early sign of disease progression. Moreover, they show a great potential in terms of non-invasive, longitudinal monitoring of cancer patients. CTCs have been extensively studied in breast cancer (BC) and were shown to present a significant phenotypic plasticity connected with initiation of epithelial-mesenchymal transition (EMT). Apart from conferring malignant properties, EMT affects CTCs recovery rate, making a significant portion of CTCs from patients’ samples undetected. Wider application of methods and markers designed to isolate and identify mesenchymal CTCs is required to expand our knowledge about the clinical impact of mesenchymal CTCs. Therefore, here we provide a comprehensive review of clinical significance of mesenchymal CTCs in BC together with statistical analysis of previously published data, in which we assessed the suitability of a number of methods/markers used for isolation of CTCs with different EMT phenotypes, both in in vitro spike-in tests with BC cell lines, as well as clinical samples. Results of spiked-in cell lines indicate that, in general, methods not based on epithelial enrichment only, capture mesenchymal CTCs much more efficiently that CellSearch® (golden standard in CTCs detection), but at the same time are not much inferior to Cell Search®, though large variation in recovery rates of added cells among the methods is observed. In clinical samples, where additional CTCs detection markers are needed, positive epithelial-based CTCs enrichment was the most efficient in isolating CTCs with mesenchymal features from non-metastatic BC patients. From the marker side, PI3K and VIM were contributing the most to detection of CTCs with mesenchymal features (in comparison to SNAIL) in non-metastatic and metastatic BC patients, respectively. However, additional data are needed for more robust identification of markers for efficient detection of CTCs with mesenchymal features.

Bioinformatics Method Was Used to Analyze the Highly Expressed Gene FAM83A of Breast Cancer in Young Women

“…Amplification tubes use the gene G3PDH as an internal reference to test the reach of FAM83A in the tumor cell line described above, PCR. The product is cloned into the T vector and sequenced in the same sequence as the gene of interest [ 34 ].…”

Epithelial‑to‑mesenchymal transition of circulating tumor cells and CD133 expression on predicting prognosis of thyroid cancer patients

“…The present study showed that the total CTCs and their subtypes had a significant clinical association with the prediction of thyroid cancer prognosis. CTCs in the blood stream can often be identified as epithelial, mesenchymal, or both mixed types according to their surface markers with different immunofluorescence stains (34,35). Studies indicate that EMT marker expression in CTCs in a number of types of cancer, such as gastric cancer, colorectal cancer, non-small cell lung cancer, breast cancer and prostate cancer are relevant to invasion and metastasis (36)(37)(38)(39).…”

Curcuminoids as Modulators of EMT in Invasive Cancers: A Review of Molecular Targets With the Contribution of Malignant Mesothelioma Studies

“…Additionally, the orchestration of multiple EMT-associated pathways and EMTassociated TFs by Forkhead box O (FOXO) proteins was also documented (Ma et al, 2018). The links with glycobiology (Pucci et al, 2021), Ca 2+ homeostasis (Jones and Hazlehurst, 2021) and the cytoskeleton (Leggett et al, 2021) were also explored, while the complexity of its interrelationships with CSCs (Roy et al, 2021), p53 (Parfenyev et al, 2021) or H 2 O 2 signaling (Milton and Konrad, 2022), and their consequences on the generation of circulating tumor cells (CTCs) (Topa et al, 2022) or occurrence of a collective invasion process (Nagai et al, 2020) were updated. Finally, as EMT is involved in such a broad range of processes associated with malignant transformation and invasiveness, it has become an increasingly interesting target for the development of new therapeutic strategies (Dudas et al, 2020;Jonckheere et al, 2022).…”