ganglioside--gd2 and Triple-Negative-Breast-Neoplasms

Triple-negative breast cancer (TNBC) is a heterogeneous disease characterized by lack of hormone receptor expression and is known for high rates of recurrence, distant metastases, and poor clinical outcomes. TNBC cells lack targetable receptors; hence, there is an urgent need for targetable markers for the disease. Breast cancer stem-like cells (BCSCs) are a fraction of cells in primary tumors that are associated with tumorigenesis, metastasis, and resistance to chemotherapy. Targeting BCSCs is thus an effective strategy for preventing cancer metastatic spread and sensitizing tumors to chemotherapy. The CD44

Topics: Biomarkers, Tumor; Carcinogenesis; Epithelial-Mesenchymal Transition; Female; Gangliosides; Humans; Neoplastic Stem Cells; Triple Negative Breast Neoplasms

Breast cancer stem-like cells (BCSC) are implicated in cancer recurrence and metastasis of triple-negative breast cancer (TNBC). We have recently discovered that ganglioside GD2 expression defines BCSCs and that ST8SIA1 regulates GD2 expression and BCSC function. In this report, we show that ST8SIA1 is highly expressed in primary TNBC; its expression is positively correlated with the expression of several BCSC-associated genes such as BCL11A, FOXC1, CXCR4, PDGFRβ, SOX2, and mutations in p53. CRISPR knockout of ST8SIA1 completely inhibited BCSC functions, including

Topics: Carcinogenesis; Cell Line, Tumor; Cell Proliferation; Gangliosides; Gene Expression Regulation, Neoplastic; Humans; Mutation; Neoplasm Metastasis; Neoplastic Stem Cells; Phenotype; Proto-Oncogene Proteins c-akt; Sialyltransferases; Signal Transduction; TOR Serine-Threonine Kinases; Triple Negative Breast Neoplasms; Tumor Suppressor Protein p53

Breast cancer (BC) is a heterogeneous disease, including different subtypes having diverse incidence, drug-sensitivity and survival rates. In particular, claudin-low and basal-like BC have mesenchymal features with a dismal prognosis. Disialoganglioside GD2 is a typical neuroectodermal antigen expressed in a variety of cancers. Despite its potential relevance in cancer diagnostics and therapeutics, the presence and role of GD2 require further investigation, especially in BC. Therefore, we evaluated GD2 expression in a cohort of BC patients and its correlation with clinical-pathological features.Sixty-three patients with BC who underwent surgery without prior chemo- and/or radiotherapy between 2001 and 2014 were considered. Cancer specimens were analyzed by immunohistochemistry and GD2-staining was expressed according to the percentage of positive cells and by a semi-quantitative scoring system.Patient characteristics were heterogeneous by age at diagnosis, histotype, grading, tumor size, Ki-67 and receptor-status. GD2 staining revealed positive cancer cells in 59% of patients. Among them, 26 cases (41%) were labeled with score 1+ and 11 (18%) with score 2+. Notably, the majority of metaplastic carcinoma specimens stained positive for GD2. The univariate regression logistic analysis revealed a significant association of GD2 with triple-receptor negative phenotype and older age (> 78) at diagnosis.We demonstrate for the first time that GD2 is highly prevalent in a cohort of BC patients clustering on very aggressive BC subtypes, such as triple-negative and metaplastic variants.

Topics: Aged; Aged, 80 and over; Biomarkers, Tumor; Breast Neoplasms; Female; Gangliosides; Humans; Immunohistochemistry; Middle Aged; Neoplasm Grading; Neoplasm Staging; Triple Negative Breast Neoplasms

Topics: Animals; Cell Line, Tumor; Female; Gangliosides; Humans; Imidazoles; Mice; Molecular Targeted Therapy; Neoplastic Stem Cells; NF-kappa B; Quinoxalines; Sialyltransferases; Signal Transduction; Triple Negative Breast Neoplasms