February 18, 2015
Major and Classification
Neuroscience and Human Development & Aging
- Michel Baudry, Ph.D.
- College of Letters, Arts, & Sciences
The Role of Calpain in Neuroblastoma Metastasis
Neuroblastoma causes one of the most common tumors in children, and by the time this disease is diagnosed, 70% of the patients’ cancer has already metastasized in other parts of their bodies, usually the bone marrow. Children are vulnerable to metastatic cancers due to active bone tissues and abundant growth factors that promote cell growth and proliferation. Consequently, multiple forms and combinations of treatments are used to treat this type of cancer, including radiation and chemotherapy. Amplification of the MCYN gene, which is expressed in many patients, results in the activation of TrkB, the tyrosine kinase receptor for brain-derived neurotrophic factor (BDNF). This has been shown to inhibit apoptosis initiated by chemotherapy, therefore making neuroblastoma cell lines resistant to chemotherapy, a feature indicating a poor prognosis for these patients. BDNF has recently been shown to activate the calcium-dependent protease calpain through MAP Kinase-mediated phosphorylation, resulting in actin polymerization, increased cell motility, and possibly increased metastatic behavior; interestingly, calpain inhibitors prevent the effect of BDNF on actin polymerization. The present study tested the hypothesis that high calpain activity resulting from TrkB stimulation correlates with increased chemoresistance in the neuroblastoma cell line. Quantitative analysis of immunoblots was used to determine the effects of BDNF and interleukin-6 (IL-6) on TrkB, ERK, and calpain pathways in different human neuroblastoma cell lines. If this hypothesis is correct, incorporating calpain inhibitors in cancer treatment could improve patient recovery.