International Journal of Molecular Sciences

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Dear Colleagues,

Nowadays, therapeutic decisions are based overwhelmingly on the pathological and molecular characterization of the primary tumor. However, metastatic lesions can be highly heterogenous and substantially different from the primary neoplasm, which hampers the efficacy of treatments. Moreover, the inaccessibility of metastatic foci and the invasiveness of a biopsy represent challenging problems and call for some other means of secondary tumor characterization. The analysis of the circulating tumor cells (CTCs) as a surrogate for metastatic lesions is non-invasive and allows for a detailed characterization of the phenotype, genotype, heterogeneity, and expression profiling, as well as a functional analysis of tumor cells. These data should have a direct impact on the diagnosis and decision-making related to adjuvant treatment by helping with patient stratification and should also provide valuable information about the biology of metastasis. This open access Special Issue will bring together original research and review articles on CTCs, their biology, methods of enumeration and characterization, role in metastasis, and predictive value for diagnostics and therapeutic applications. It will provide a platform to share new discoveries, approaches, and technical developments in the field of CTC research for the development of the next generation of anti-metastasis treatments.

Topics of this Special Issue include, but are not limited to

Diagnostic and therapeutic applications of CTC research;
The biology of CTCs in different cancer types;
CTC mobilization by treatment;
Phenotypic/genotypic heterogeneity of CTCs;
Technical developments in the isolation, enumeration, and characterization of CTCs;
Functional analysis of CTCs, including culture and CDX;
CTC analysis in single-cell resolution;
Cell-free DNA vs. CTC;
Epithelial/hybrid/mesenchymal properties of CTCs;
CTC clusters: biology, enumeration, role in metastasis.

Dr. Ewa Grzybowska
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

CTC
metastasis
tumor heterogeneity
invasion
single-cell analysis
cancer dissemination
circulation
treatment response
CTC clusters

Published Papers (2 papers)

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Research

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16 pages, 2459 KiB

Open AccessArticle

CD47 Expression in Circulating Tumor Cells and Circulating Tumor Microemboli from Non-Small Cell Lung Cancer Patients Is a Poor Prognosis Factor

by Jacqueline Aparecida Torres, Angelo Borsarelli Carvalho Brito, Virgilio Souza e Silva, Iara Monique Messias, Alexcia Camila Braun, Anna Paula Carreta Ruano, Marcilei E. C. Buim, Dirce Maria Carraro and Ludmilla Thomé Domingos Chinen

Int. J. Mol. Sci. 2023, 24(15), 11958; https://doi.org/10.3390/ijms241511958 - 26 Jul 2023

Cited by 1 | Viewed by 1238

Abstract

Circulating tumor cells (CTCs) and/or circulating tumor microemboli (CTM) from non-small cell lung cancer (NSCLC) patients may be a non-invasive tool for prognosis, acting as liquid biopsy. CTCs interact with platelets through the transforming growth factor-β/transforming growth factor-β receptor type 1 (TGF-β/TGFβRI) forming clusters. CTCs also may express the Cluster of Differentiation 47 (CD47) protein, responsible for the inhibition of phagocytosis, the “don’t eat me” signal to macrophages. Objectives: To isolate, quantify and analyze CTCs/CTMs from metastatic NSCLC patients, identify TGFβRI/CD47 expression in CTCs/CTMs, and correlate with progression-free survival (PFS). Methods: Blood (10 mL) was collected at two time-points: T1 (before the beginning of any line of treatment; T2 (60 days after initial collection). CTCs were isolated using ISET^®. Immunocytochemistry was conducted to evaluate TGFβRI/CD47 expression. Results: 45 patients were evaluated. CTCs were observed in 82.2% of patients at T1 (median: 1 CTC/mL; range: 0.33–11.33 CTCs/mL) and 94.5% at T2 (median: 1.33 CTC/mL; 0.33–9.67). CTMs were observed in 24.5% of patients and significantly associated with poor PFS (10 months vs. 17 months for those without clusters; p = 0.05) and disease progression (p = 0.017). CTMs CD47+ resulted in poor PFS (p = 0.041). TGFβRI expression in CTCs/CTMs was not associated with PFS. Conclusion: In this study, we observed that CTC/CTM from NSCLC patients express the immune evasion markers TGFβRI/CD47. The presence of CTMs CD47+ is associated with poor PFS. This was the first study to investigate CD47 expression in CTCs/CTM of patients with NSCLC and its association with poor PFS. Full article

(This article belongs to the Special Issue Circulating Tumor Cells: Pathological, Molecular and Functional Characteristics 4.0)

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Review

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27 pages, 1173 KiB

Open AccessReview

Exploring the Immunological Profile in Breast Cancer: Recent Advances in Diagnosis and Prognosis through Circulating Tumor Cells

by Amalia Kotsifaki, Sousanna Maroulaki and Athanasios Armakolas

Int. J. Mol. Sci. 2024, 25(9), 4832; https://doi.org/10.3390/ijms25094832 - 29 Apr 2024

Viewed by 728

Abstract

This review offers a comprehensive exploration of the intricate immunological landscape of breast cancer (BC), focusing on recent advances in diagnosis and prognosis through the analysis of circulating tumor cells (CTCs). Positioned within the broader context of BC research, it underscores the pivotal role of the immune system in shaping the disease’s progression. The primary objective of this investigation is to synthesize current knowledge on the immunological aspects of BC, with a particular emphasis on the diagnostic and prognostic potential offered by CTCs. This review adopts a thorough examination of the relevant literature, incorporating recent breakthroughs in the field. The methodology section succinctly outlines the approach, with a specific focus on CTC analysis and its implications for BC diagnosis and prognosis. Through this review, insights into the dynamic interplay between the immune system and BC are highlighted, with a specific emphasis on the role of CTCs in advancing diagnostic methodologies and refining prognostic assessments. Furthermore, this review presents objective and substantiated results, contributing to a deeper understanding of the immunological complexity in BC. In conclusion, this investigation underscores the significance of exploring the immunological profile of BC patients, providing valuable insights into novel advances in diagnosis and prognosis through the utilization of CTCs. The objective presentation of findings emphasizes the crucial role of the immune system in BC dynamics, thereby opening avenues for enhanced clinical management strategies. Full article

(This article belongs to the Special Issue Circulating Tumor Cells: Pathological, Molecular and Functional Characteristics 4.0)

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