High GD2 expression defines breast cancer cells with enhanced invasiveness

Mansoori, Maryam; Roudi, Raheleh; Abbasi, Ata; Abolhasani, Maryam; Rad, Isa Abdi; Shariftabrizi, Ahmad; Madjd, Zahra

doi:10.1016/j.yexmp.2019.05.001

Cited by 29 publications

(29 citation statements)

References 40 publications

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“…This finding suggests that CD24 is associated with the aggressive phenotype of breast cancer cells. These results were consistent with a previous study that concluded that higher expression of CD24 was correlated with more advanced histological grade of breast tumors and lymph node involvement [25]. Similarly, Chen et al reported that CD24 expression was not significantly associated with tumor characteristics, however, it was significantly associated with other poor prognostic variables such as negative hormone receptors and positive HER2 and triple-negative (TN) phenotype [20].…”

Section: Discussionsupporting

confidence: 91%

TP53 Mutation in Saudi Breast Cancer Patients: Correlations with Cancer Stem Cell Markers Expression and Clinicopathological Variables

Nassir¹,

Elmoneim²,

Esheba³

et al. 2020

SJPM

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Background: Breast cancer is one of the most common cancers with a high mortality rate worldwide including Saudi Arabia. It is characterized by the presence of both intra-and inter-tumor heterogeneity. It describes the origin of this heterogeneity to the cancer stem cells (CSC). Breast cancer stem cells are characterized by the expression of the surface markers CD44 and lack or very low expression of CD24. Objectives: To assess cancer stem cell markers (CD44 andCD24) in 126 breast cancer cases by immunohistochemistry and study their association with a different type of TP53 gene mutations by applying next-generation sequencing (NGS). In addition to analyze the association between these markers and the clinicopathological characteristics. Results: CD44 expression was significantly associated with lymph node metastasis, tumor grade, stage (each P<0.0001), and ER expression (P = 0.016). CD24 expression was found to be associated with lymph node metastasis and ER only. For the molecular analysis, the number of mutations per case was significantly associated with the advanced stage of breast cancer (p = 0.004). Also, missense mutation was highly associated with CD44 and CD24 (p=0.04, p=0.005), respectively. Stop-gained mutation and Frameshift mutation both were associated with CD44 only (p=0.01, p=0.05), respectively. Finally, the synonymous mutation was only associated with the stage of cancer (p=0.01). Conclusion, we believe that the combination of CD44, CD24, TP53 and TP53 gene mutations can be prognostic factors for breast cancer patients and the information obtained may contribute to the development of a treatment.

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Section: Discussionsupporting

confidence: 91%

TP53 Mutation in Saudi Breast Cancer Patients: Correlations with Cancer Stem Cell Markers Expression and Clinicopathological Variables

Nassir¹,

Elmoneim²,

Esheba³

et al. 2020

SJPM

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“…14 15 A recent analysis of a primary breast cancer tissue microarray demonstrated a strong association between high GD2 expression and advanced cancer stage; it also demonstrated correlations between high GD2 expression and larger tumor size and nodal invasion. 16 In other solid tumors, such as small cell lung cancer and osteosarcoma, GD2 enhances tumor proliferation and invasiveness. 17 18 In addition to its function as a marker for BCSCs, its tumor-specific expression and stability after binding to a specific antibody makes GD2 an excellent target for antibody-based therapy.…”

Section: Introductionmentioning

confidence: 99%

Anti-GD2 antibody dinutuximab inhibits triple-negative breast tumor growth by targeting GD2⁺ breast cancer stem-like cells

Anand

El-Dana

et al. 2021

J Immunother Cancer

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BackgroundTriple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype with no effective standard therapy. Breast cancer stem-like cells (BCSCs) in primary TNBCs are reported to be responsible for metastatic spread of the disease and resistance to chemotherapy, but no available therapeutic tools target BCSCs. We previously reported that the ganglioside GD2 is highly expressed on BCSCs and that inhibition of its expression hampers TNBC growth. We therefore hypothesized that the anti-GD2 antibody dinutuximab (ch14.18) targets GD2+ BCSCs and inhibits TNBC growth.MethodTo test our hypothesis, we first determined GD2 expression via immunohistochemistry in frozen primary tumor samples from patients with TNBC (n=89). Then, we examined the effects of dinutuximab on TNBC cell adhesion, migration, and mammosphere formation in vitro and on tumor growth in vivo using TNBC cell-line and patient-derived xenograft (PDX) models.ResultsWe found that GD2 was expressed in around 60% of primary TNBC tumors at variable levels and was associated with worse overall survival of patients with TNBC (p=0.002). GD2 was found to be expressed in tumors and stroma, but normal ducts and lobules in adjacent tissues have shown low or no GD2 staining, indicating that GD2 is potentially a novel biomarker for tumor and its microenvironment. Treatment with dinutuximab significantly decreased adhesion and migration of MDA-MB-231 and SUM159 TNBC cells. Moreover, dinutuximab treatment inhibited mTOR signaling, which has been shown to be regulated by GD2 in BCSCs. Dinutuximab also reduced tumor growth in nude mice bearing TNBC cell-line xenografts. Finally, dinutuximab in combination with activated natural killer cells inhibited tumor growth in a TNBC PDX model and improved overall survival of tumor-bearing mice.ConclusionsDinutuximab successfully eliminated GD2+ cells and reduced tumor growth in both in vivo models. Our data provide proof-of-concept for the criticality of GD2 in BCSCs and demonstrate the potential of dinutuximab as a novel therapeutic approach for TNBC.

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“…Farida et al 12 and Jang et al 13 reported that CD44 expression is not correlated with histopathological grading in breast cancer. Otherwise, Moansoori et al 14 and McFarlane et al 15 reported a significant positive correlation between CD44 expression with histological grade. Breast cancer samples with advance histological grade also had higher CD44 expression.…”

Section: Discussionmentioning

confidence: 94%

Correlation between CD44 expression on histopathological grading, metastasis, survival overall (SO) and disease free survival (DFS) on women breast cancer

et al. 2020

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Breast cancer is one of the health problems in the world. In Indonesia, it was highest prevalence of cancer in 2018. CD44, a non-kinase transmembrane glycoprotein, plays an important role in cancer development and progression. It is responsible for mediating of the adhesion between adjacent cells andal so between cells and the extracellular matrix. The aim of study was to investigate the relationship between the CD44 expressionand histopathological grading, metastasis, overall survival (OS) as well as disease free survival (DFS) in breast cancer patients.This was a retrospective cross sectional study using data on medical records of breast cancer cases at Dr. Wahidin Sudirohusodo General Hospital, Makasar from 2016 to 2018. Examination of CD44 expression were performed from paraffin block samples. Data of the CD44 expression and medical records obtained were then presented in tables and statistically analyzed using chi-squared and Kaplan-Meier survival analysis. No significantly relationship between the CD44 expression and histopathological grading was reported (p>0.05). However, significantly relationship between the CD44 expression and metastasis war reported (p<0.01). Patients with metastasis having high CD44 expression was significantly higher (90%) than those patients without metastasis (60%) (p<0.01). No significantly relationship between the CD44 expression and OS or DFS was reported (p>0.05). In conclusion, there is relationship between CD44 expression and metastasis in the breast cancer patients. However, there is norelationship between CD44 expression and histopathological grading, OS as well as DFS.

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High GD2 expression defines breast cancer cells with enhanced invasiveness

Cited by 29 publications

References 40 publications

TP53 Mutation in Saudi Breast Cancer Patients: Correlations with Cancer Stem Cell Markers Expression and Clinicopathological Variables

TP53 Mutation in Saudi Breast Cancer Patients: Correlations with Cancer Stem Cell Markers Expression and Clinicopathological Variables

Anti-GD2 antibody dinutuximab inhibits triple-negative breast tumor growth by targeting GD2⁺ breast cancer stem-like cells

Correlation between CD44 expression on histopathological grading, metastasis, survival overall (SO) and disease free survival (DFS) on women breast cancer

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High GD2 expression defines breast cancer cells with enhanced invasiveness

Cited by 29 publications

References 40 publications

TP53 Mutation in Saudi Breast Cancer Patients: Correlations with Cancer Stem Cell Markers Expression and Clinicopathological Variables

TP53 Mutation in Saudi Breast Cancer Patients: Correlations with Cancer Stem Cell Markers Expression and Clinicopathological Variables

Anti-GD2 antibody dinutuximab inhibits triple-negative breast tumor growth by targeting GD2+ breast cancer stem-like cells

Correlation between CD44 expression on histopathological grading, metastasis, survival overall (SO) and disease free survival (DFS) on women breast cancer

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Anti-GD2 antibody dinutuximab inhibits triple-negative breast tumor growth by targeting GD2⁺ breast cancer stem-like cells