Functional Analysis of Viable Circulating Tumor Cells from Triple-Negative Breast Cancer Patients Using TetherChip Technology

Vardas, Vasileios; Ju, Julia A.; Christopoulou, Athina; Xagara, Anastasia; Georgoulias, Vassilis; Κotsakis, Athanasios; Alix‐Panabières, Catherine; Martin, Stuart S.; Kallergi, Galatea

doi:10.3390/cells12151940

Cited by 3 publications

(4 citation statements)

References 42 publications

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“…VRB also induced autophagocytosis and reduced the scratch-healing rate effectively in all cell lines, while further demonstrating variable efficacy across the NSCLC cells. The results here are in line with previous results from our lab and literature [51][52][53]. VRB has been well documented to produce variable effects in cancer therapy, owing to both, the type of tumor and its respective genetic profile, and the administration pattern of the drug [54][55][56].…”

Section: Discussionsupporting

confidence: 92%

Vinorelbine Alters lncRNA Expression in Association with EGFR Mutational Status and Potentiates Tumor Progression Depending on NSCLC Cell Lines’ Genetic Profile

Alsharoh,

Chiroi,

Nutu

et al. 2023

Biomedicines

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Lung cancer remains the leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) as the most common type. In addition, NSCLC has a high mortality rate and an overall adverse patient outcome. Although significant improvements have been made in therapeutic options, effectiveness is still limited in late stages, so the need for a better understanding of the genomics events underlying the current therapies is crucial to aid future drug development. Vinorelbine (VRB) is an anti-mitotic chemotherapy drug (third-generation vinca alkaloid) used to treat several malignancies, including NSCLC. However, despite its widespread clinical use, very little is known about VRB-associated genomic alterations in different subtypes of NSCLC. This article is an in vitro investigation of the cytotoxic effects of VRB on three different types of NSCLC cell lines, A549, Calu-6, and H1792, with a closer focus on post-treatment genetic alterations. Based on the obtained results, VRB cytotoxicity produces modifications on a cellular level, altering biological processes such as apoptosis, autophagy, cellular motility, cellular adhesion, and cell cycle, but also at a genomic level, dysregulating the expression of some coding genes, such as EGFR, and long non-coding RNAs (lncRNAs), including CCAT1, CCAT2, GAS5, MALAT1, NEAT1, NORAD, XIST, and HOTAIR, that are implicated in the mitogen-activated protein kinase (MAPK) signaling pathway. Therefore, although extensive validation is required, these results pave the way towards a better understanding of the cellular and genomic alterations underlying the cytotoxicity of VRB.

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Section: Discussionsupporting

confidence: 92%

Vinorelbine Alters lncRNA Expression in Association with EGFR Mutational Status and Potentiates Tumor Progression Depending on NSCLC Cell Lines’ Genetic Profile

Alsharoh,

Chiroi,

Nutu

et al. 2023

Biomedicines

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“…It has been shown that CTCs may have a great predictive value in detecting activating mutations, such as epidermal growth factor receptor (EGFR) and EML4-ALK fusion protein, that may be superior to ctDNA analysis [28,29]. We have also shown that live CTCs can be used for functional analysis and evaluation of drug efficacy using TetherChip technology [30].…”

Section: Discussionmentioning

confidence: 99%

ES-SCLC Patients with PD-L1+ CTCs and High Percentages of CD8+PD-1+T Cells in Circulation Benefit from Front-Line Immunotherapy Treatment

Xagara,

Roumeliotou,

Kokkalis

et al. 2024

Biomedicines

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SCLC is an aggressive cancer type with high metastatic potential and bad prognosis. CTCs are a valuable source of tumor cells in blood circulation and are among the major contributors to metastasis. In this study we evaluated the number of CTCs that express PD-L1 in treatment-naïve ES-SCLC patients receiving ICI in a front-line setting. Moreover, we explored the percentages of different immune T-cell subsets in circulation to assess their potential role in predicting responses. A total of 43 patients were enrolled—6 of them with LS-SCLC, and 37 with ES-SCLC disease. In addition, PBMCs from 10 healthy donors were used as a control group. Different T-cell subtypes were examined through multicolor FACS analysis and patients’ CTCs were detected using immunofluorescence staining. SCLC patients had higher percentages of PD-1-expressing CD3+CD4+ and CD3+CD8+ T-cells, as well as elevated PD-1 protein expression compared to healthy individuals. Additionally, in ES-SCLC patients, a positive correlation between CD3+CD8+PD-1+ T-cells and PD-L1+ CTCs was detected. Importantly, patients harboring higher numbers of CD3+CD8+PD-1+ T-cells together with PD-L1+CTCs had a survival advantage when receiving front-line immunotherapy. Thus, this study proposes, for first time possible, immune cell–CTCs interaction, as well as a potential novel clinical biomarker for ICI responses in ES-SCLC patients.

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“…10 Unfortunately, the generation of heterogeneous CTCs occurs when cancer cells undergo epithelial-to-mesenchymal transition (EMT) during migration, which seriously compromises the accurate detection of CTCs. 11,12 Previous researches have shown that EMT is fairly common in tumors and plays an important role in tumor metastasis, making tumor cells more aggressive, drug-resistant, and metastasizing. 13,14 Therefore, it is very meaningful and urgent to establish efficient detection methods to address the challenge of heterogeneous CTCs.…”

Section: Introductionmentioning

confidence: 99%

“…Circulating tumor cells (CTCs) are tumor cells that spontaneously circulate in the peripheral blood after separating from primary or metastatic tumors. − Efficient enrichment and analysis of CTCs can facilitate real-time tumor dynamics monitoring, therapeutic effect evaluation, and real-time individual treatment implementation. , Various methods have been developed to detect CTCs, such as microfluidic chips, immunomagnetic beads, polymerase chain reactions, and immunofluorescence staining . Unfortunately, the generation of heterogeneous CTCs occurs when cancer cells undergo epithelial-to-mesenchymal transition (EMT) during migration, which seriously compromises the accurate detection of CTCs. , Previous researches have shown that EMT is fairly common in tumors and plays an important role in tumor metastasis, making tumor cells more aggressive, drug-resistant, and metastasizing. , Therefore, it is very meaningful and urgent to establish efficient detection methods to address the challenge of heterogeneous CTCs.…”

Section: Introductionmentioning

confidence: 99%

Engineered Leukocyte Biomimetic Colorimetric Sensor Enables High-Efficient Detection of Tumor Cells Based on Bioorthogonal Chemistry

Li,

Jia,

Zhu

et al. 2024

ACS Appl. Mater. Interfaces

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Accurate detection of heterogeneous circulating tumor cells (CTCs) is critical as they can make tumor cells more aggressive, drug-resistant, and metastasizing. Although the leukocyte membrane coating strategy is promising in meeting the challenge of detecting heterogeneous CTCs due to its inherent antiadhesive properties, it is still limited by the reduction or loss of expression of known markers. Bioorthogonal glycol-metabolic engineering is expected to break down this barrier by feeding the cells with sugar derivatives with a unique functional group to establish artificial targets on the surface of tumor cells. Herein, an engineered leukocyte biomimetic colorimetric sensor was accordingly fabricated for high-efficient detection of heterogeneous CTCs. Compared with conventional leukocyte membrane coating, the sensor could covalently bound to the heterogeneous CTCs models fed with Ac 4 ManNAz in vitro through the synergy of bioorthogonal chemistry and metabolic glycoengineering, ignoring the phenotypic changes of heterogeneous CTCs. Meanwhile, a sandwich structure composed of leukocyte biomimetic layer/CTCs/MoS 2 nanosheet was formed for visual detection of HeLa cells as low as 10 cells mL −1 . Overall, this approach can overcome the dependence of conventional cell membrane biomimetic technology on specific cell phenotypes and provide a new viewpoint to highly efficiently detect heterogeneous CTCs.

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Functional Analysis of Viable Circulating Tumor Cells from Triple-Negative Breast Cancer Patients Using TetherChip Technology

Cited by 3 publications

References 42 publications

Vinorelbine Alters lncRNA Expression in Association with EGFR Mutational Status and Potentiates Tumor Progression Depending on NSCLC Cell Lines’ Genetic Profile

Vinorelbine Alters lncRNA Expression in Association with EGFR Mutational Status and Potentiates Tumor Progression Depending on NSCLC Cell Lines’ Genetic Profile

ES-SCLC Patients with PD-L1+ CTCs and High Percentages of CD8+PD-1+T Cells in Circulation Benefit from Front-Line Immunotherapy Treatment

Engineered Leukocyte Biomimetic Colorimetric Sensor Enables High-Efficient Detection of Tumor Cells Based on Bioorthogonal Chemistry

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