Surface marker profiling of SH-SY5Y cells enables small molecule screens identifying BMP4 as a modulator of neuroblastoma differentiation.

摘要: Neuroblastoma is the most common extra-cranial solid tumor in children. Its broad spectrum of clinical outcomes reflects underlying inherent cellular heterogeneity. As current treatments often do not lead to eradication, there a need better define therapy-resistant neuroblastoma and identify new modulatory molecules. To this end, we performed first comprehensive flow cytometric characterization surface molecule expression cell lines. Exploiting an established clustering algorithm (SPADE) for unbiased visualization subsets, conducted multiwell screen small modulators phenotype. In addition SH-SY5Y cells, SH-EP, BE(2)-M17 Kelly lines were included follow-up analysis as vitro models neuroblastoma. A combinatorial detection glycoprotein epitopes (CD15, CD24, CD44, CD57, TrkA) chemokine receptor CXCR4 (CD184) enabled quantitative identification SPADE-defined clusters differentially responding Exposure bone morphogenetic protein (BMP)-4 was found enhance TrkAhigh/CD15−/CD184− subset, accompanied by reduction doublecortin-positive neuroblasts NMYC cells. Beyond yielding novel marker candidates studying pathology, our approach may provide tools improved pharmacological screens towards developing avenues diagnosis treatment.