Neuroblastoma (NB) is the most common extra-cranial solid tumor in children. Recently
discovered neuroblastoma tumor-initiating cells (NB-TICs) have many properties of cancer stem
cells and form tumors with as few as 10 cells. To elucidate the signaling pathways driving NB-
TIC survival and proliferation, we surveyed the phospho-tyrosine containing subset of the NB-
TIC proteome. Over 300 phosphorylated proteins were identified, including 21 tyrosine kinases
of which several belong to the Src kinase family. Using bioinformatics tools, several
hematopoietic signaling pathways were identified, including the B cell receptor (BCR) pathway. Further proteomic approaches substantiated molecular hematopoietic features in NB-TICs.
Inhibitors of BCR proximal kinases SYK and SFKs were cytotoxic to NB-TICs. Clinically
utilized inhibitors of SFKs induce apoptosis in NB-TICs. Targeting hematopoietic survival
pathways in NB-TICs from the bone marrow, which have thus far not been predicted to play a role in this neural malignancy, may provide new drug therapies for NB.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/30136 |
| Date | 30 November 2011 |
| Creators | Vojvodic, Milijana |
| Contributors | Kaplan, David, Moran, Michael |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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