Neuroblastoma tumors have a hierarchy of tumor initiating cells reflecting neural crest development

Abstract

A number of different tumors have been shown to contain subsets of cells that have tumor forming capability, known as tumor initiating cells (TICs). We have established neuroblastoma TICs (NTIC) from primary neuroblastoma tumors and from bone marrow metastases. These cell lines genetically resemble the tumor of origin. A number of these NTIC cell lines express markers of committed neuroendocrine sympathoadrenal cells such as TH and DBH. We found that other cell lines are partially or completely devoid of these neuroendocrine markers and instead show expression of markers of the early neural crest including NESTIN, SOX10/SOX9 (SOX-E proteins), CD24, CD133 and NOTCH. Some combinations of the markers are reflective of cells of the pre-migratory neural crest. Our data suggests that the developmental hierarchy of the neural crest is retained in the tumor. We will present data on the developmental classification, the developmental plasticity and response of the NTICs to external differentiation clues.