This study examined the effect of CD24 on anoikis of ovarian cancer cells. The expression of CD24 was detected by RT-PCR and Western blotting in ovarian cancer cells with high metastatic potential (HO-8910PM cells) and low metastatic potential (A2780 cells). Cell viability and cell proliferation were detected by MTT assay in suspension culture and adhesion culture. Soft agar culture was used to observe the colony formation. Anoikis was flow cytometrically detected. The results showed that the expression levels of CD24 mRNA and protein were significantly higher in HO-8910PM cells than in A2780 cells (P<0.01). In the suspension culture and soft agar culture, the HO-8910PM cells formed larger and more colonies (35.33 ± 5.51 vs. 16.67 ± 4.04; P<0.01), and showed a stronger resistance to anoikis than A2780 cells did (cell apoptosis rate: 5.93% ± 2 .38% vs. 16.32% ± 2.00%; P<0.01). After treated with CD24 monoclonal antibodies, the number of colony formed in HO-8910PM and A2780 cells was significantly decreased (9.33 ± 2.52 and 8.00 ± 2.00, respectively), and the anoikis rate of the two cell lines was also markedly increased (23.11% ± 2.87% and 28.36% ± 2.29%, respectively). Our study suggested that CD24 may play an important role in the development of anoikis resistance and CD24 can be used as a new therapeutic target to induce anoikis and inhibit metastasis in ovarian cancer.
Anoikis ; CD24 Antigen ; genetics ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; Cell Survival ; Drug Resistance, Neoplasm ; Female ; Humans ; Ovarian Neoplasms ; genetics ; metabolism

OBJECTIVE: To evaluate the association between CD24 polymorphism and genetic susceptibility to breast cancer in Chongqing women of Han nationality. METHODS: In the case-control study, single nucleotide polymorphism of CD24 (rs3838646 and rs52812045) was genotyped by Sequenom MassArray®iPLEX GOLD System in 170 patients with breast cancer and 178 healthy controls. Data were analyzed via t test, Chi-square test, and logistic regression analysis. RESULTS: The distribution of CD24 rs3838646 genotype and allelotype had no significant difference between the patients with breast cancer and healthy controls (χ2=3.54, P=0.17; χ2=2.29, P=0.13). Stratified by menstruation status, premenopausal individuals carrying CD24 rs3838646 Del allele significantly reduced the risk (OR=0.51, 95% CI 0.26-1.00, P=0.0485) of breast cancer compared with the individuals carrying CD24 CA/CA genotype. The distribution of CD24 rs52812045 genotypes and allelotypes had no significant difference between the patients with breast cancer and healthy controls (χ2=5.37, P=0.07; χ2=3.05, P=0.08). Compared with C/C homozygotes, CD24 rs52812045 T/T homozygotes had a significantly reduced risk (OR=0.47, 95% CI 0.23-0.95; P=0.04) for breast cancer. CONCLUSION CD24 polymorphism may be a marker for susceptibility to breast cancer in Han population in southwestern China. CD24 polymorphisms may be associated with a reduced risk of breast cancer in Chinese population. Further studies are needed to confirm these findings.
Asian Continental Ancestry Group ; Breast Neoplasms ; genetics ; CD24 Antigen ; genetics ; Case-Control Studies ; China ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; Polymorphism, Single Nucleotide

Objective: To investigate the expression of CD24 gene in human malignant pleural mesothelioma (MPM) cells and tissues, and evaluate its relationship with clinicopathological characteristics and clinical prognosis of MPM patients. Methods: In February 2021, UALCAN database was used to analyze the correlation between CD24 gene expression and clinicopathological characteristics in 87 cases of MPM patients. The TIMER 2.0 platform was used to explore the relationship between the expression of CD24 in MPM and tumor immune infiltrating cells. cBioportal online tool was used to analyze the correlation between CD24 and MPM tumor marker gene expression. RT-qPCR was used to analyze the expressions of CD24 gene in human normal pleural mesothelial cell lines LP9 and MPM cell lines NCI-H28 (epithelial type), NCI-H2052 (sarcoma type), and NCI-H2452 (biphasic mixed type). RT-qPCR was performed to detect the expressions of CD24 gene in 18 cases of MPM tissues and matched normal pleural tissues. The expression difference of CD24 protein in normal mesothelial tissue and MPM tissue was analyzed by immunohistochemistry. A Kaplan-Meier model was constructed to explore the influence of CD24 gene expression on the prognosis of MPM patients, and Cox regression analysis of prognostic factors in MPM patients was performed. Results: The CD24 gene expression without TP53 mutation MPM patients was significantly higher than that of patients in TP53 mutation (P<0.05). The expression of CD24 gene in MPM was positively correlated with B cells (r(s)=0.37, P<0.001). The expression of CD24 gene had a positive correlation with the expressions of thrombospondin 2 (THBS2) (r(s)=0.26, P<0.05), and had a negative correlation with the expression of epidermal growth factor containing fibulin like extracellular matrix protein 1 (EFEMP1), mesothelin (MSLN) and calbindin 2 (CALB2) (r(s)=-0.31, -0.52, -0.43, P<0.05). RT-qPCR showed that the expression level of CD24 gene in MPM cells (NCI-H28, NCI-H2052 and NCI-H2452) was significantly higher than that in normal pleural mesothelial LP9 cells. The expression level of CD24 gene in MPM tissues was significantly higher than that in matched normal pleural tissues (P<0.05). Immunohistochemistry showed that the expressions of CD24 protein in epithelial and sarcoma MPM tissues were higher than those of matched normal pleural tissues. Compared with low expression of CD24 gene, MPM patients with high expression of CD24 gene had lower overall survival (HR=2.100, 95%CI: 1.336-3.424, P<0.05) and disease-free survival (HR=1.800, 95%CI: 1.026-2.625, P<0.05). Cox multivariate analysis showed that compared with the biphasic mixed type, the epithelial type was a protective factor for the prognosis of MPM patients (HR=0.321, 95%CI: 0.172-0.623, P<0.001). Compared with low expression of CD24 gene, high expression of CD24 gene was an independent risk factor for the prognosis of MPM patients (HR=2.412, 95%CI: 1.291-4.492, P=0.006) . Conclusion: CD24 gene and protein are highly expressed in MPM tissues, and the high expression of CD24 gene suggests poor prognosis in MPM patients.
Humans ; Mesothelioma, Malignant ; Mesothelioma/diagnosis* ; Lung Neoplasms/genetics* ; Pleural Neoplasms/diagnosis* ; Prognosis ; Biomarkers, Tumor/analysis* ; Extracellular Matrix Proteins ; CD24 Antigen/genetics*

OBJECTIVETo investigate the effect of tricostantin A (TSA) on self-renewal of breast cancer stem cells and explore the mechanisms.

METHODSBreast cancer cell lines MDA-MB-468, MDA-MB-231, MCF-7 and SKBR3 were cultured in suspension and treated with different concentrations of TSA for 7 days, using 0.1% DMSO as the control. Secondary mammosphere formation efficiency and percentage of CD44(+)/CD24(-) sub-population in the primary mammospheres were used to evaluate the effects of TSA on self-renewal of breast cancer stem cells. The breast cancer stem cell surface marker CD44(+)/CD24(-) and the percentage of apoptosis in the primary mammospheres were assayed using flow cytometry. The mRNA expressions of Nanog, Sox2 and Oct4 in the primary mammospheres were assayed with quantitative PCR.

RESULTSTSA at both 100 and 500 nmol/L, but not at 10 nmol/L, partially inhibited the self-renewal of breast cancer stem cells from the 4 cell lines. TSA at 500 nmol/L induced cell apoptosis in the primary mammospheres. TSA down-regulated the mRNA expression of Nanog and Sox2 in the primary mammospheres.

CONCLUSIONTSA can partially inhibit the self-renewal of breast cancer stem cells through a mechanism involving the down-regulation of Nanog and Sox2 expression, indicating the value of combined treatments with low-dose TSA and other anticancer drugs to achieve maximum inhibition of breast cancer stem cell self-renewal. The core transcriptional factor of embryonic stem cells Nanog and Sox2 can be potential targets of anticancer therapy.

Antineoplastic Agents ; administration & dosage ; pharmacology ; Apoptosis ; drug effects ; Breast Neoplasms ; metabolism ; pathology ; CD24 Antigen ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Dose-Response Relationship, Drug ; Down-Regulation ; Female ; Histone Deacetylase Inhibitors ; administration & dosage ; pharmacology ; Homeodomain Proteins ; genetics ; metabolism ; Humans ; Hyaluronan Receptors ; metabolism ; Hydroxamic Acids ; administration & dosage ; pharmacology ; Nanog Homeobox Protein ; Neoplastic Stem Cells ; metabolism ; pathology ; RNA, Messenger ; metabolism ; SOXB1 Transcription Factors ; genetics ; metabolism