Cancer Stem Cells and Their Interaction with the Tumor Microenvironment in Neuroblastoma

Abstract

Neuroblastoma, a solid tumor arising from neural crest cells, accounts for over 15% of all pediatric cancer deaths. The interaction of neuroblastoma cancer-initiating cells with their microenvironment likely plays an integral role in the maintenance of resistant disease and tumor relapse. In this review, we discuss the interaction between neuroblastoma cancer-initiating cells and the elements of the tumor microenvironment and how these interactions may provide novel therapeutic targets for this difficult to treat disease.

Keywords: cancer stem cell; cancer-associated fibroblasts; hypoxia; neuroblastoma.

Figure 1

Neuroblastoma tumor microenvironment and potential sites of therapy. (1) Embryonal signaling pathways (e.g., Notch, Hedgehog, Wnt); (2) cancer stem cell (CSC) surface marker-directed therapy (e.g., CD133, CD114, nestin, etc.); (3) selective inhibition of CSCs (e.g., DECA-14, rapamycin); (4) differentiation therapy (e.g., retinoic acid, proteasome inhibitors); (5) blocking angiogenesis/VEGF/VEGFR (e.g., Bevacizumab); (6) immunotherapy and immune activation (e.g., lenalidomide, ch14.18, GM-CSF, IL-2); (7) blocking chemokine/receptor function (e.g., CXCL12/CXCR4/CXCR7 chemokine axis). TAM, tumor-associated macrophage; MDSC, myeloid-derived suppressor cell; CAF, cancer-associated fibroblast.