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CD24 - a Novel Target for Cancer Therapy and a Biomarker for Cancer Prediction

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A special issue of Journal of Personalized Medicine (ISSN 2075-4426). This special issue belongs to the section "Clinical Medicine, Cell, and Organism Physiology".

Deadline for manuscript submissions: closed (25 June 2021) | Viewed by 39078

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Prof. Dr. Nadir Arber

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Guest Editor

Health Promotion Center and Integrated Cancer Prevention Center, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
Interests: cancer treatment; early detection; chemoprevention; personalized medicine; immuno- and gene- therapy; genetics; big data
Special Issues, Collections and Topics in MDPI journals

Dr. Shiran Shapira

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Guest Editor

The Integrated Cancer Prevention Center, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel
Interests: liquid biopsy; cancer; screening; prevention; early detection; antibody engineering, gene therapy, exosomes, drug development
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

CD24 was first described in the early 1980s and only attributed to scattered publications. Since then, as evidence of its importance, more and more researchers with diverse interests have encountered CD24. CD24 is a small, glycophosphatidylinositol-anchored cell surface receptor with a diverse array of functions; when adaptive immunity, inflammation, autoimmunity and cancer are just some of them. CD24 gene and protein expression is highly dynamic in response to cellular differentiation and stimulation in a cell-specific manner. Furthermore, CD24 interacts with a diverse collection of ligands, including cell adhesion molecules and transmembrane proteins. CD24 has a role in the adaptive immune response, discriminating danger and pathogen-associated molecular patterns and carcinogenesis. It is overexpressed in many cancers and appears oncogenic. It is expressed in many human malignancies, hematological as well as in a wide array of solid tumors. In recent years, CD24 gene has raised considerable interest in tumor biology and poor treatment outcome. It has been identified as a new prognostic factor, stem cell marker in the human neoplasm and a biomarker for early detection of cancer.

CD24 expression causes the acquisition of multiple cellular properties associated with tumor growth, metastasis and chemo-resistant. The biology of CD24 is intriguing but still not completely understood.

With this special issue on CD24, we wish to stimulate increased awareness of this tiny gene and summarize the major findings associated with CD24 to stimulate new ideas for further research that may reveal the underlying link among the diverse processes mediated by CD24. Therefore we are soliciting for new original and exiciting manuscripts that will shed light on its crucial role and potential applications in pathological and healthy situations.

Prof. Nadir Arber
Dr. Shiran Shapira
Guest Editors

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. Journal of Personalized Medicine is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

CD24
Cancer therapy
Cancer prediction and diagnosing
Biomarker and Target
CD24 and inflammation
CD24 and cytokine storm
CD24 and corona

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Published Papers (9 papers)

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Research

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20 pages, 4216 KiB

Open AccessArticle

Renal Tubular CD24 Upregulation Aggravates Folic Acid Induced Acute Kidney Injury: A Possible Role for T Regulatory Cells Inhibition in Mice

by Moshe Shashar, Doron Schwartz, Asia Zubkov, Sarit Hoffman, Lior Jankelson, Shiran Shapira, Barak Merimsky, Julia Berman, Tamara Chernichovski, Oeren Amitai, Michal Ariela Raz, Rami Hershkovitz, Ayelet Grupper, Talia Weinstein, Nadir Arber and Idit. F. Schwartz

J. Pers. Med. 2023, 13(7), 1134; https://doi.org/10.3390/jpm13071134 - 13 Jul 2023

Viewed by 1532

Abstract

Acute kidney injury (AKI) is characterized by cell death and inflammation. CD24 is a protein induced during tissue damage and is not expressed in mature renal tissue. We explored the role of CD24 in the pathogenesis of folic acid-induced AKI (FA-AKI) in mice. A single Intraperitoneal (IP) injection of folic acid induced AKI in WT and CD24^−/− mice. Renal function tests, histological analysis, immunohistochemistry, Western blot analysis, and ELISA were performed to assess the severity of renal damage and the intensity of the inflammatory response. FA-AKI induced CD24 in the distal tubular epithelial cells. Compared to WT mice, FA-AKI CD24^−/− mice exhibited an attenuated reduction in renal function and histological injury, lower serum IL-10 and interferon γ, and decreased expression of renal TNFα. In contrast, renal and systemic IL-33 upregulation were augmented. CD24^−/− FA-AKI animals exhibited increased splenic margination and renal infiltration of regulatory T cells (Tregs). At day 7, FA-AKI CD24^−/− mice exhibited increased expression of tubular pro-apoptotic and decreased anti-apoptotic proteins compared to WT animals. Anti-CD24 antibody administration to FA-AKI mice attenuated the decrease in renal function as well as the histological injury. Renal biopsies from patients with ATN stained strongly for CD24 in the distal tubules. In conclusion, during AKI, upregulation of CD24 promotes renal inflammation through inhibition of Treg infiltration and diversion of cell death towards necrosis rather than apoptosis. Neutralization of CD24 may prove a target for future therapies in AKI. Full article

(This article belongs to the Special Issue CD24 - a Novel Target for Cancer Therapy and a Biomarker for Cancer Prediction)

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9 pages, 341 KiB

Open AccessArticle

Predictors of the CD24/CD11b Biomarker among Healthy Subjects

by Shiran Shapira, Gal Aiger, Amitay Ohayon, Dina Kazanov, Fatin Mdah, Marina Ben Shimon, Mori Hay-Levy, Lian Banon, Ido Laskov, Jacob Mashiah, Shahar Lev-Ari and Nadir Arber

J. Pers. Med. 2021, 11(9), 939; https://doi.org/10.3390/jpm11090939 - 21 Sep 2021

Cited by 3 | Viewed by 2470

Abstract

The CD24 gene has raised considerable interest in tumor biology as a new prognostic factor and a biomarker for the early detection of cancer. There are currently no studies that assess predictors of CD24 in blood tests among healthy individuals. Our aims were (1) to evaluate predictors of the CD24/CD11b biomarker among healthy subjects and (2) to assess CD24/CD11b levels of participants with and without benign tumors. Our cohort included 1640 healthy subjects, aged 20–85, recruited at the Health Promotion and Integrated Cancer Prevention Center (ICPC) in the Tel Aviv Medical Center. Eligible subjects completed a detailed questionnaire on medical history and other epidemiologic information. CD24/CD11b expression in peripheral blood leukocytes (PBLs) obtained from blood samples of participants was analyzed by flow cytometry. Our results showed that the average levels of CD24/CD11b in healthy patients (22.8 ± 9.3) was statistically significant lower compared to subjects with benign cancers (26.1 ± 10.5, p < 0.001). Our multivariable analysis demonstrated that elevated levels of CRP (coefficient β: 1.98, p = 0.011) were significantly associated with high levels of CD24/CD11b expression among healthy participants. Other risk factors of cancer were not associated with elevated CD24 levels among healthy subjects. In conclusion, our findings may assist in further development and optimization of the CD24/CD11b biomarker to serve as a cancer screening test for early detection of cancer among the healthy population. Full article

(This article belongs to the Special Issue CD24 - a Novel Target for Cancer Therapy and a Biomarker for Cancer Prediction)

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9 pages, 2782 KiB

Open AccessArticle

Feasibly of CD24/CD11b as a Screening Test for Hematological Malignancies

by Shiran Shapira, Dina Kazanov, Fatin Mdah, Hadas Yaakobi, Yair Herishanu, Chava Perry, Irit Avivi, Gilad Itchaki, Adi Shacham-Abulafia, Pia Raanani, Mori Hay-Levy, Gal Aiger, Jacob Mashiah, Shahar Lev-Ari and Nadir Arber

J. Pers. Med. 2021, 11(8), 724; https://doi.org/10.3390/jpm11080724 - 27 Jul 2021

Cited by 7 | Viewed by 2404

Abstract

An estimated 1.24 million blood cancer cases occur annually worldwide, accounting for approximately 6% of all cancer cases. Currently, there are no standardized hematology cancer screening tests that are recommended for the general population. CD24 is a mucin-like cell surface molecule and P-selectin ligand, which plays a significant role in the maturation of B-lymphocytes and was found to be overexpressed in a number of hematological malignancies. Our primary aim was to assess the sensitivity and specificity of the CD24/CD11b-based blood test for the detection of hematological malignancies. Our cohort included 488 subjects with positive hematological cancer diagnosis (n = 122) and healthy subjects (n = 366). CD24/CD11b expression in peripheral blood leukocytes (PBLs) obtained from blood samples of participants was analyzed by flow cytometry. Our results demonstrated that the average levels of CD24/CD11b in healthy patients (21.7 ± 9.0) were statistically significantly lower compared to levels of CD24/CD11b in cancer patients (29.5 ± 18.7, p < 0.001). The highest levels of CD24/CD11b were found in multiple myeloma (39.1 ± 23.6), followed by chronic myeloid leukemia (33.0 ± 13.7) and non-Hodgkin lymphoma (32.3 ± 13.3). The test had an overall sensitivity for hematologic cancers of 78.5% (95% CI, 70.7–86.3%) and specificity of 80.2% (95% CI, 76.1–84.3%). In conclusion, our findings indicate the feasibility of a CD24/CD11b-based blood test as a screening test of hematological malignancies. Full article

(This article belongs to the Special Issue CD24 - a Novel Target for Cancer Therapy and a Biomarker for Cancer Prediction)

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15 pages, 10793 KiB

Open AccessArticle

A Comparative in Silico Analysis of CD24’s Prognostic Value in Human and Canine Prostate Cancer

by Antonio Fernando Leis-Filho, Patrícia de Faria Lainetti, Mayara Simão Franzoni, Chiara Palmieri, Priscila Emiko Kobayshi, Renee Laufer-Amorim and Carlos Eduardo Fonseca-Alves

J. Pers. Med. 2021, 11(3), 232; https://doi.org/10.3390/jpm11030232 - 23 Mar 2021

Cited by 6 | Viewed by 2926

Abstract

CD24 is a cell surface molecule anchored by glycosyl-phosphatidyl-inositol and expressed by different human cancers, including prostate cancer (PC). Some studies have demonstrated that CD24 expression is associated with poor patient outcome; however, few studies have investigated CD24 expression in spontaneous animal models of human PC, such as canine PC. This study aimed to evaluate the expression of CD24 in human PC using the in silico analysis of the data obtained from The Cancer Genome Atlas (TCGA) and comparing it with the previously published prostatic canine transcriptome data. In addition, CD24 expression was confirmed by immunohistochemistry in an independent cohort of canine prostatic samples and its prognostic significance assessed. The systematic review identified 10 publications fitting with the inclusion criteria of this study. Of the 10 manuscripts, 5 demonstrated a direct correlation between CD24 overexpression and patient prognoses. CD24 expression was also associated with PSA relapse (2/5) and tumor progression (1/5). However, the in silico analysis did not validate CD24 as a prognostic factor of human PC. Regarding canine PC, 10 out of 30 normal prostates and 27 out of 40 PC samples were positive for CD24. As in humans, there was no association with overall survival. Overall, our results demonstrated a significant CD24 overexpression in human and canine prostate cancer, although its prognostic value may be questionable. However, tumors overexpressing CD24 may be a reliable model for new target therapies and dogs could be used of a unique preclinical model for these studies. Full article

(This article belongs to the Special Issue CD24 - a Novel Target for Cancer Therapy and a Biomarker for Cancer Prediction)

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11 pages, 2393 KiB

Open AccessArticle

Behavioral Characterizing of CD24 Knockout Mouse—Cognitive and Emotional Alternations

by Keren Nitzan, Roni Toledano, Shiran Shapira, Nadir Arber and Ravid Doron

J. Pers. Med. 2021, 11(2), 105; https://doi.org/10.3390/jpm11020105 - 6 Feb 2021

Cited by 2 | Viewed by 3588

Abstract

CD24 is a small, glycophosphatidylinositol-anchored cell surface protein, mostly investigated with respect to cancer, inflammation, and autoimmune diseases. CD24 knockdown or inhibition has been used to test various biochemical mechanisms and neurological conditions; however, the association between CD24 and behavioral phenotypes has not yet been examined. This study aims to characterize cognitive and emotional functions of CD24 knockout mice (CD24^−/− )compared with CD24 wild-type mice at three time-points: adolescence, young adulthood, and adulthood. Our results show that CD24^−/− mice exhibited better cognitive performance and less anxiety-like behavior compared with WT mice, with no effect on depression-like behavior. This phenotype was constant from childhood (2 months old) to adulthood (6 months old). The results from our study suggest that CD24 may influence important behavioral aspects at the whole-organism level, which should be taken into consideration when using CD24 knockout models. Full article

(This article belongs to the Special Issue CD24 - a Novel Target for Cancer Therapy and a Biomarker for Cancer Prediction)

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17 pages, 3957 KiB

Open AccessArticle

High Expression Level of PPARγ in CD24 Knockout Mice and Gender-Specific Metabolic Changes: A Model of Insulin-Sensitive Obesity

by Shiran Shapira, Dina Kazanov, Rachel Dankner, Sigal Fishman, Naftali Stern and Nadir Arber

J. Pers. Med. 2021, 11(1), 50; https://doi.org/10.3390/jpm11010050 - 15 Jan 2021

Cited by 5 | Viewed by 6582

Abstract

Background: The heat-stable HSA/CD24 gene encodes a protein that shows high expression levels in adipocyte precursor cells but low levels in terminally differentiated adipocytes. Its high expression in many types of human cancer suggests an association between cancer, diabetes, and obesity, which is currently unclear. In addition, peroxisome proliferator-activated receptor gamma (PPARγ) is a regulator of adipogenesis that plays a role in insulin sensitivity, lipid metabolism, and adipokine expression in adipocytes. Aim: To assess gender-dependent changes in CD24 KO and its association with PPARγ expression. Experimental approach: WT and CD24 KO mice were monitored from birth up to 12 months, and various physiological and molecular characteristics were analysed. Mean body weight and adipose mass were higher in KO mice than in WT mice. Male, but not female, KO mice showed increased insulin sensitivity, glucose uptake, adipocyte size, and PPARγ expression than WT mice. In addition, enteric bacterial populations, assessed through high-throughput sequencing of stool 16S rRNA genes, were significantly different between male KO and WT mice. Conclusions: CD24 may negatively regulate PPARγ expression in male mice. Furthermore, the association between the CD24 and insulin sensitivity suggests a possible mechanism for diabetes as a cancer risk factor. Finally, CD24 KO male mice may serve as a model of obesity and insulin hyper-sensitivity. Full article

(This article belongs to the Special Issue CD24 - a Novel Target for Cancer Therapy and a Biomarker for Cancer Prediction)

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Review

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15 pages, 345 KiB

Open AccessEditor’s ChoiceReview

CD24: A Novel Target for Cancer Immunotherapy

by Emmanouil Panagiotou, Nikolaos K. Syrigos, Andriani Charpidou, Elias Kotteas and Ioannis A. Vathiotis

J. Pers. Med. 2022, 12(8), 1235; https://doi.org/10.3390/jpm12081235 - 28 Jul 2022

Cited by 44 | Viewed by 7122

Abstract

Cluster of differentiation 24 (CD24) is a small, highly glycosylated cell adhesion protein that is normally expressed by immune as well as epithelial, neural, and muscle cells. Tumor CD24 expression has been linked with alterations in several oncogenic signaling pathways. In addition, the CD24/Siglec-10 interaction has been implicated in tumor immune evasion, inhibiting macrophage-mediated phagocytosis as well as natural killer (NK) cell cytotoxicity. CD24 blockade has shown promising results in preclinical studies. Although there are limited data on efficacy, monoclonal antibodies against CD24 have demonstrated clinical safety and tolerability in two clinical trials. Other treatment modalities evaluated in the preclinical setting include antibody–drug conjugates and chimeric antigen receptor (CAR) T cell therapy. In this review, we summarize current evidence and future perspectives on CD24 as a potential target for cancer immunotherapy. Full article

(This article belongs to the Special Issue CD24 - a Novel Target for Cancer Therapy and a Biomarker for Cancer Prediction)

8 pages, 236 KiB

Open AccessReview

CD24 for Cardiovascular Researchers: A Key Molecule in Cardiac Immunology, Marker of Stem Cells and Target for Drug Development

by Eyal Sagiv and Michael A. Portman

J. Pers. Med. 2021, 11(4), 260; https://doi.org/10.3390/jpm11040260 - 1 Apr 2021

Cited by 5 | Viewed by 2305

Abstract

The study of the membrane protein, CD24, and its emerging role in major disease processes, has made a huge leap forward in the past two decades. It appears to have various key roles in oncogenesis, tumor progression and metastasis, stem cell maintenance and immune modulation. First described in the 1980s as the homologous human protein to the mouse HSA (Heat Stable Antigen), it was reported as a surface marker in developing hematopoietic cell lines. The later discovery of its overexpression in a large number of human neoplasms, lead cancer researchers to discover its various active roles in critical checkpoints during cancer development and progression. Targeting CD24 in directed drug development showed promising results in cancer treatment. More recently, the chimeric CD24-Fc protein has shown exciting results in clinical trials as a specific modulator of auto-inflammatory syndromes. This report is aimed to summarize the relevant literature on CD24 and tie it together with recent advancements in cardiovascular research. We hypothesize that CD24 is a promising focus of research in the understanding of cardiovascular disease processes and the development of novel biological therapies. Full article

(This article belongs to the Special Issue CD24 - a Novel Target for Cancer Therapy and a Biomarker for Cancer Prediction)

18 pages, 1022 KiB

Open AccessReview

The Emerging Role of CD24 in Cancer Theranostics—A Novel Target for Fluorescence Image-Guided Surgery in Ovarian Cancer and Beyond

by Katrin Kleinmanns, Vibeke Fosse, Line Bjørge and Emmet McCormack

J. Pers. Med. 2020, 10(4), 255; https://doi.org/10.3390/jpm10040255 - 27 Nov 2020

Cited by 10 | Viewed by 6911

Abstract

Complete cytoreductive surgery is the cornerstone of the treatment of epithelial ovarian cancer (EOC). The application of fluorescence image-guided surgery (FIGS) allows for the increased intraoperative visualization and delineation of malignant lesions by using fluorescently labeled targeting biomarkers, thereby improving intraoperative guidance. CD24, a small glycophosphatidylinositol-anchored cell surface receptor, is overexpressed in approximately 70% of solid cancers, and has been proposed as a prognostic and therapeutic tumor-specific biomarker for EOC. Recently, preclinical studies have demonstrated the benefit of CD24-targeted contrast agents for non-invasive fluorescence imaging, as well as improved tumor resection by employing CD24-targeted FIGS in orthotopic patient-derived xenograft models of EOC. The successful detection of miniscule metastases denotes CD24 as a promising biomarker for the application of fluorescence-guided surgery in EOC patients. The aim of this review is to present the clinical and preclinically evaluated biomarkers for ovarian cancer FIGS, highlight the strengths of CD24, and propose a future bimodal approach combining CD24-targeted fluorescence imaging with radionuclide detection and targeted therapy. Full article

(This article belongs to the Special Issue CD24 - a Novel Target for Cancer Therapy and a Biomarker for Cancer Prediction)

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