human cortical neuronal cells hcn 2  (ATCC)

Journal: Nature cancer

Article Title: Transition to a mesenchymal state in neuroblastoma confers resistance to anti-GD2 antibody via reduced expression of ST8SIA1

doi: 10.1038/s43018-022-00405-x

Figure Lengend Snippet: a , Flow cytometry panel showing GD2 expression in low-passage (p + 3), primary cortical neurons (HCN-001) and the mesenchymal neuroblastoma cell line SK-N-AS after treatment with tazemetostat. b , Mean fluorescence intensity measurements for groups shown in ( n = 3). Data are shown as mean ± s.d. Significance was determined by one-way ANOVA and Tukey’s post-hoc test. c , Immunohistochemistry showing GD2 staining in the mouse cortex of mice treated for 28 days with 350 mg kg −1 tazemetostat ( n = 3) or control ( n = 3). Uninvolved human tissue from matched human cortex and GD2-expressing human diffuse intrinsic pontine glioma (DIPG) tumor sections are included as controls for low and high GD2 expression, respectively. GD2 expression is stained in blue, and H3K27M (human tissue only) is stained in brown. d , Schema showing proposed mechanism of GD2 regulation. GD2 is highly expressed on the cell surface of neuroblastoma cells expressing an adrenergic transcriptional program. Transition from an adrenergic state to a mesenchymal state decreases GD2 expression through downregulation of ST8SIA1 , rendering cells nonresponsive to anti-GD2 immunotherapy. Treatment with an EZH2 inhibitor induces an adrenergic-like state through transcriptional, epigenetic and chromatin remodeling, thereby re-expressing ST8SIA1 , increasing GD2 expression and restoring sensitivity to anti-GD2 antibody. Representative data from flow cytometry were confirmed in two independent experiments.

Article Snippet: Primary human cortical neurons HCN-001 were purchased from NEUROMICS.

Techniques: Flow Cytometry, Expressing, Fluorescence, Immunohistochemistry, Staining