Platelets, immune cells and the coagulation cascade; friend or foe of the circulating tumour cell? DOI Creative Commons
Mark P. Ward, Laura Kane, Lucy Norris

и другие.

Molecular Cancer, Год журнала: 2021, Номер 20(1)

Опубликована: Март 31, 2021

Abstract Cancer cells that transit from primary tumours into the circulatory system are known as circulating tumour (CTCs). These cancer have unique phenotypic and genotypic characteristics which allow them to survive within circulation, subsequently extravasate metastasise. CTCs emerged a useful diagnostic tool using “liquid biopsies” report on metastatic potential of cancers. However, by their nature interact with components blood constant basis, influencing both physical morphological well capabilities. properties associated molecular profile may provide critical prognostic capabilities in clinic. Platelets minutes dissemination crucial formation initial niche. coagulation proteins also alter fate CTC EMT, promoting pro-survival signalling aiding evading immune cell destruction. capacity directly hijack utilise aid seeding processes. The disruption clusters offer strategy for treatment advance staged Therapeutic these heterotypical interactions direct targeting hold great promise, especially advent new immunotherapies personalised medicines. Understanding role platelets, cascade play biology will us identify characterise most clinically relevant patients. This clinical utility diagnosis/prognosis.

Язык: Английский

Next-generation sequencing to guide cancer therapy DOI
Jeffrey Gagan, Eliezer M. Van Allen

Genome Medicine, Год журнала: 2015, Номер 7(1)

Опубликована: Июль 28, 2015

Язык: Английский

Процитировано

265
Expression and function of epithelial cell adhesion molecule EpCAM: where are we after 40 years? DOI Creative Commons
Olivier Gires, Min Pan,

Henrik Schinke

и другие.

Cancer and Metastasis Reviews, Год журнала: 2020, Номер 39(3), С. 969 - 987

Опубликована: Июнь 7, 2020

Abstract EpCAM (epithelial cell adhesion molecule) was discovered four decades ago as a tumor antigen on colorectal carcinomas. Owing to its frequent and high expression carcinomas their metastases, serves prognostic marker, therapeutic target, an anchor molecule circulating disseminated cells (CTCs/DTCs), which are considered the major source for metastatic cancer cells. Today, is reckoned multi-functional transmembrane protein involved in regulation of adhesion, proliferation, migration, stemness, epithelial-to-mesenchymal transition (EMT) carcinoma To fulfill these functions, instrumental intra- intercellular signaling full-length following regulated intramembrane proteolysis, generating functionally active extra- intracellular fragments. Intact proteolytic fragments interact with claudins, CD44, E-cadherin, epidermal growth factor receptor (EGFR), components WNT Ras/Raf pathways, respectively. This plethora functions contributes shaping intratumor heterogeneity partial EMT, determinants clinical outcome patients. represents marker epithelial status primary systemic emerges measure capacity CTCs. Consequentially, has reclaimed potential target

Язык: Английский

Процитировано

259
Circulating biomarkers for early detection and clinical management of colorectal cancer DOI Creative Commons

María Marcuello,

Veronika Vymetálková, Rui P. Neves

и другие.

Molecular Aspects of Medicine, Год журнала: 2019, Номер 69, С. 107 - 122

Опубликована: Июнь 14, 2019

New non-invasive approaches that can complement and improve on current strategies for colorectal cancer (CRC) screening management are urgently needed. A growing number of publications have documented components tumors, which shed into the circulation, be detected in form liquid biopsies used to detect CRC at early stages, predict response certain therapies recurrence a minimally invasive way. The analysis circulating tumor DNA (ctDNA), tumor-derived cells (CTC, cells) or microRNA (miRNA) blood other body fluids, great potential different aspects management. challenge now is find types components, biofluids detection methods would most suitable applied steps treatment. This chapter will provide an up date review ctDNA, CTCs miRNAs as new biomarkers CRC, either clinical detection, highlighting their advantages limitations.

Язык: Английский

Процитировано

244
Clinical applications of the CellSearch platform in cancer patients DOI
Sabine Riethdorf,

Linda O′Flaherty,

Claudia Hille

и другие.

Advanced Drug Delivery Reviews, Год журнала: 2018, Номер 125, С. 102 - 121

Опубликована: Фев. 1, 2018

Язык: Английский

Процитировано

243
Epithelial-to-mesenchymal transition leads to loss of EpCAM and different physical properties in circulating tumor cells from metastatic breast cancer DOI Open Access
Kyung‐A Hyun, Gi‐Bang Koo,

Hyunju Han

и другие.

Oncotarget, Год журнала: 2016, Номер 7(17), С. 24677 - 24687

Опубликована: Март 22, 2016

The dissemination of circulating tumor cells (CTCs) requires the Epithelial-to-Mesenchymal transition (EMT), in which lose their epithelial characteristics and acquire more mesenchymal-like phenotypes. Current isolation CTCs relies on affinity-based approaches reliant expression Epithelial Cell Adhesion Molecule (EpCAM). Here we show EMT-induced breast cancer maintained prolonged mammosphere culture conditions possess increased EMT markers stem cell markers, as well reduced mass size by quantitative phase microscopy; however, EpCAM is dramatically decreased these cells. Moreover, isolated from patients using a label-free microfluidic flow fractionation device had differing patterns EpCAM, indicating that affinity may underestimate CTC number potentially miss critical subpopulations. Further characterization CTCs, including low-EpCAM populations, this technology improve detection techniques diagnosis, ultimately improving treatment.

Язык: Английский

Процитировано

242
Profiling circulating tumour cells and other biomarkers of invasive cancers DOI
Mahla Poudineh, Edward H. Sargent, Klaus Pantel

и другие.

Nature Biomedical Engineering, Год журнала: 2018, Номер 2(2), С. 72 - 84

Опубликована: Фев. 3, 2018

Язык: Английский

Процитировано

227
Circulating tumor cell isolation, culture, and downstream molecular analysis DOI Creative Commons
Sandhya Sharma,

Rachel Zhuang,

Marisa Long

и другие.

Biotechnology Advances, Год журнала: 2018, Номер 36(4), С. 1063 - 1078

Опубликована: Март 18, 2018

Язык: Английский

Процитировано

220
Optimization and Evaluation of a Novel Size Based Circulating Tumor Cell Isolation System DOI Creative Commons
Lei Xu, Xueying Mao, Ahmet Imrali

и другие.

PLoS ONE, Год журнала: 2015, Номер 10(9), С. e0138032 - e0138032

Опубликована: Сен. 23, 2015

Isolation of circulating tumor cells (CTCs) from peripheral blood has the potential to provide a far easier "liquid biopsy" than tissue biopsies, monitor cell populations during disease progression and in response therapies. Many CTC isolation technologies have been developed. We optimized Parsortix system, an epitope independent, size compressibility-based platform for CTCs isolation, making it possible harvest at speed sample volume comparable standard CellSearch system. captured more half cancer different lines spiked samples healthy donors using this Cell loss immunostaining transferred fixed on slides is major problem analyzing rare samples. developed novel transfer fixation method retain >90% slide after immunofluorescence process without affecting signal strength specificity. Using method, we evaluated system prostate patients comparison immunobead based systems IsoFlux CellSearch. harvested similar number (p = 0.33) cytokeratin (CK) positive 7.5 mL 10 (an average 33.8 37.6 respectively). The purity by 3.1% was significantly higher 1.0% 0.02). CK 0.04) seven patient samples, where both were utilized 32.1 10.1 also clusters Parsortix. four-color found that 85.8% PC3 expressed EpCAM, 91.7% 2.5% lacked epithelial markers. Interestingly, 95.6% Vimentin, including those marker expression, indicating epithelial-to-mesenchymal transition. CK-positive/Vimentin-positive/CD45-negative, CK-negative/Vimentin-positive/CD45-negative observed four five but rarely three controls, harvests with mesenchymal features. demonstrated DU145 spiking experiment viable culture.

Язык: Английский

Процитировано

213
Circulating and disseminated tumor cells: harbingers or initiators of metastasis? DOI Creative Commons

Arko Dasgupta,

Andrea R. Lim, Cyrus M. Ghajar

и другие.

Molecular Oncology, Год журнала: 2017, Номер 11(1), С. 40 - 61

Опубликована: Янв. 1, 2017

Tumor cells leave the primary tumor and enter circulation. Once there, they are called circulating (CTCs). A fraction of CTCs capable entering distant sites persisting as disseminated (DTCs). An even smaller DTCs progressing toward metastases. It is known that DTC microenvironment plays an important role in sustaining their survival, regulating growth, conferring resistance to therapy. But we still have much learn about nature these rare cell populations predict which will progress what exactly should cause concern for future relapse. Although recent technological advances our ability detect molecularly functionally characterize promise unravel this ambiguity, timing dissemination precise source profiled impact conclusions can be made from endeavors. In review, discuss biology DTCs; technologies detect, isolate, profile cells; exceptions must apply understanding play metastatic process. We conclude a greater effort understand unique context positively use outcome, monitor treatment efficacy, reveal therapeutically relevant targets deplete ultimately prevent metastasis.

Язык: Английский

Процитировано

203
Epithelial-type systemic breast carcinoma cells with a restricted mesenchymal transition are a major source of metastasis DOI Creative Commons
Xiao Liu, Junjian Li, Bruno L. Cadilha

и другие.

Science Advances, Год журнала: 2019, Номер 5(6)

Опубликована: Июнь 1, 2019

Carcinoma cells undergo epithelial-mesenchymal transition (EMT); however, contributions of EMT heterogeneity to disease progression remain a matter debate. Here, we addressed the status ex vivo cultured circulating and disseminated tumor (CTCs/DTCs) in syngeneic mouse model metastatic breast cancer (MBC). Epithelial-type CTCs with restricted mesenchymal had strongest lung metastases formation ability, whereas mesenchymal-type showed limited ability. EpCAM expression served as surrogate marker evaluate clinical samples from MBC, including metastases, CTCs, DTCs. The proportion epithelial-type especially DTCs, correlated distant poorer outcome patients MBC. This study fosters our understanding metastasis underpins heterogeneous phenotypes important parameters for prognosis treatment. We further suggest that EpCAM-dependent CTC isolation systems will underestimate numbers but quantify clinically relevant cells.

Язык: Английский

Процитировано

183