Clinical Relevance of Mesenchymal- and Stem-Associated Phenotypes in Circulating Tumor Cells Isolated from Lung Cancer Patients

Pantazaka, Evangelia; Vardas, Vasileios; Roumeliotou, Argyro; Kakavogiannis, Stavros; Kallergi, Galatea

doi:10.3390/cancers13092158

Cited by 28 publications

(27 citation statements)

References 74 publications

(118 reference statements)

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“…An immunosuppressive tumour microenvironment is a sanctuary for primary tumours [ 31 ]. However, as the tumour cells proliferate, some cells slough off the edges of a tumor and enter the circulatory system, only a few CTCs survive in the active immune surveillance environment [ 8 , 32 ]. These surviving CTCs can accumulate to form circulating tumour microemboli (CTM).…”

Section: Discussionmentioning

confidence: 99%

“…Most tumour cells die rapidly after entering peripheral blood circulation owing to hypoxia, immune recognition and other factors. Only a few CTCs with stem-cell-like characteristics survive [ 8 ], which can accumulate to form a tiny tumour thrombus, breaking through the vascular wall and invading distant organs. CTCs proliferate and metastasise to target organs with an appropriate microenvironment if they can evade recognition by the immune system.…”

Section: Introductionmentioning

confidence: 99%

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Novel Circulating Tumour Cell-Related Risk Model Indicates Prognosis and Immune Infiltration in Lung Adenocarcinoma

Liang

Liu

Jiang

et al. 2022

Journal of Immunology Research

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Background. Lung adenocarcinoma (LUAD) is the most common histological subtype of lung cancer (LC) and one of the leading causes of cancer-related death worldwide. LUAD has a low survival rate owing to tumour invasion and metastasis. Circulating tumour cells (CTCs) are precursors of distant metastasis, which are considered to adopt the characteristics of cancer stem cells (CSCs). Therefore, analysing the risk factors of LUAD from the perspective of CTCs may provide novel insights into the metastatic mechanisms and may help to develop diagnostic and therapeutic strategies. Methods. A total of 447 patients from TCGA dataset were included in the training cohort, and 460 patients from the GEO dataset were included in the validation cohort. A CTC-related-gene risk model was constructed using LASSO penalty–Cox analysis, and its predictive value was further verified. Functional enrichment analysis was performed on differentially expressed genes (DEGs), followed by immune correlation analysis based on the results. In addition, western blot, CCK-8 and colony formation assays were used to validate the biological function of RAB26 in LUAD. Results. A novel in-silico CTC-related-gene risk model, named the CTCR model, was constructed, which successfully divided patients into the high- and low-risk groups. The prognosis of the high-risk group was worse than that of the low-risk group. ROC analysis revealed that the risk model outperformed traditional clinical markers in predicting the prognosis of patients with LUAD. Further study demonstrated that the identified DEGs were significantly enriched in immune-related pathways. The immune score of the low-risk group was higher than that of the high-risk group. In addition, RAB26 was found to promote the proliferation of LUAD. Conclusion. A prognostic risk model based on CTC-related genes was successfully constructed, and the relationship between DEGs and tumour immunity was analysed. In addition, RAB26 was found to promote the proliferation of LUAD cells.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Novel Circulating Tumour Cell-Related Risk Model Indicates Prognosis and Immune Infiltration in Lung Adenocarcinoma

Liang

Liu

Jiang

et al. 2022

Journal of Immunology Research

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“…During the EMT process, the percentage of MSC subpopulation in tumor microenvironment increased. MSCs produce vimentin, N-cadherin, fibronectin, matrix metalloproteinases, integrins, and smooth muscle actin, which form a foundation of the tumor extracellular matrix [57,58]. MSCs also expressed chemokines involved in the enrollment of immune cells and stromal cells towards increasing tumor cell mobility and overcoming the venous barrier during neovascularization across EMT.…”

Section: Tumor Stromamentioning

confidence: 99%

Clinical Application Perspectives of Lung Cancers 3D Tumor Microenvironment Models for In Vitro Cultures

Wieleba

Wojas‐Krawczyk

Krawczyk

et al. 2022

IJMS

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Despite the enormous progress and development of modern therapies, lung cancer remains one of the most common causes of death among men and women. The key element in the development of new anti-cancer drugs is proper planning of the preclinical research phase. The most adequate basic research exemplary for cancer study are 3D tumor microenvironment in vitro models, which allow us to avoid the use of animal models and ensure replicable culture condition. However, the question tormenting the scientist is how to choose the best tool for tumor microenvironment research, especially for extremely heterogenous lung cancer cases. In the presented review we are focused to explain the key factors of lung cancer biology, its microenvironment, and clinical gaps related to different therapies. The review summarized the most important strategies for in vitro culture models mimicking the tumor–tumor microenvironmental interaction, as well as all advantages and disadvantages were depicted. This knowledge could facilitate the right decision to designate proper pre-clinical in vitro study, based on available analytical tools and technical capabilities, to obtain more reliable and personalized results for faster introduction them into the future clinical trials.

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“…[ 34 ] In addition to undergoing EMT, the discovery of CCSCs provides an alternative phenotype for allowing CTCs survive and metastasize. [ 35 ] Thus, the detection of CCSCs in the circulation seems to be more important than CTCs.…”

Section: Different Types Of Circulating Cancer‐related Cells Have The...mentioning

confidence: 99%

The Discovery of Novel Circulating Cancer‐Related Cells in Circulation Poses New Challenges to Microfluidic Devices for Enrichment and Detection

Huang

Zhou

et al. 2022

Small Methods

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cells (CTCs) are precursors of metastasis in various cancers. They are detached cells slough off the edges of a solid tumor, and then enter the bloodstream or lymphatic system, moving from the primary site to distal organs via the lymphatic channels or the circulation. Although an estimated number of 3.2 × 10 6 tumor cells detach from one gram of tumor tissues per day, [2] CTCs have a relatively short life span that most of them begin to apoptosis within 24 h due to the loss of adhesion to the extracellular matrix, the shear forces of blood flow, or attacks from the immune cells. [3,4] Only a tiny fraction of CTCs that have undergone epithelial-mesenchymal transition (EMT) or CTC clusters formation survive in the bloodstream. [5] After EMT, epithelial CTCs acquire a mesenchymal phenotype, and become invasive and motile. CTCs hold the genetic information of the primary tumor, due to their same origin, thus can act as the surrogate of primary tumor for the monitoring of tumor phenotype/genotype. [6] CTCs counts have been reported correlate to overall survival and/or metastatic relapse, and suggested as a surrogate predictive marker for early diagnoses, the evaluation of chemotherapy efficacy, and cancer prognosis. [7] However, CTCs detection and analysis have two major challenges: their rarity in a typically sampled blood volume (10-50 mL), as well as genetical and phenotypical heterogeneity. [8] Thus, enrichment and detection procedures are the foundation for developing the technologies of CTCs detection. Microfluidic chip is a promising technology for CTCs isolation, identification, and characterization by using their biological and physical properties. It owes unique advantages, such as low-cost, simplicity, reduction in reagent consumption, miniaturization, fast and precise control.The substantial heterogeneity of CTCs determines their variability in expression patterns, [9] which causes difficulties to define a CTC by using specific markers. The most widely used markers to identify CTCs are EpCAM and cytokeratins (CKs). Thus, a long time in the early days, CTCs are defined as EpCAM or CKs positive and CD45 negative. But only epithelial CTCs express these two proteins. CTCs undergoing EMT gradually lose their epithelial features, having no or very low expression of epithelial markers (e.g., EpCAM, CKs, Circulating tumor cells (CTCs) enumeration has been widely used as a surrogate predictive marker for early diagnoses, the evaluation of chemotherapy efficacy, and cancer prognosis. Microfluidic technologies for CTCs enrichment and detection have been developed and commercialized as automation platforms. Currently, in addition to CTCs, some new types of circulating cancer-related cells (e.g., CCSCs, CTECs, CAMLs, and heterotypic CTC clusters) in circulation are also reported to be correlated to cancer diagnosis, metastasis, or prognosis. And they widely differ from the conventional CTCs in positive markers, cellular morphology, or size, which presents a new technological challenge to microfluidic devices that use ...

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Clinical Relevance of Mesenchymal- and Stem-Associated Phenotypes in Circulating Tumor Cells Isolated from Lung Cancer Patients

Cited by 28 publications

References 74 publications

Novel Circulating Tumour Cell-Related Risk Model Indicates Prognosis and Immune Infiltration in Lung Adenocarcinoma

Novel Circulating Tumour Cell-Related Risk Model Indicates Prognosis and Immune Infiltration in Lung Adenocarcinoma

Clinical Application Perspectives of Lung Cancers 3D Tumor Microenvironment Models for In Vitro Cultures

The Discovery of Novel Circulating Cancer‐Related Cells in Circulation Poses New Challenges to Microfluidic Devices for Enrichment and Detection

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