Dissection Of The Mechanisms Of Iron Metabolism Of Human Neuroblastoma And The Use Of Innovative Iron-Binding Drugs As Novel Anti-Cancer Therapeutics
Brief description:
Neuroblastoma (NB) is an aggressive and the most common extracranial solid tumor of childhood with a 17-month median age of diagnosis. Interestingly, the serum ferritin level of patients was found to be related to the prognosis of NB patients, with high levels suggesting a poor prognosis and low levels a good prognosis. Research has demonstrated that the intracellular iron concentration of NB cells is extremely higher than other types of cancer cells and this extremely high level of iron concentration indicates the unusual up-taken and metabolism of iron in cells. The previous research confirmed that the transferrin receptor 1 (TfR1), which is involved in the up-taken of iron from transferrin, can also help cells obtain iron from extracellular ferritin. Our latest results show that the upregulation of iron concentration leads to the increase of CD63 levels in fibroblast cells, which means more exosomes will be formed. My project focuses on the iron metabolism of human neuroblastoma and tries to dissect the mechanisms of the regulation of iron metabolism and its effects on cancer cell proliferation and metastasis. This includes but not limits to the iron up-taken and secretion in NB cells, the role of MYC family expression in iron metabolism, the crosstalk between MYC and other genes that participated in iron metabolism, and the relationship between iron metabolism and cancer cell metastasis. Moreover, since the current chemotherapy to NB, which is an iron chelator, desferrioxamine (DFO), is limited by the long i.v. or s.c. infusions required to produce significant Fe excretion and is very expensive, the development of new chemotherapy remains critical. Our group has developed various compounds which perform encouraging anti-proliferation activity against NB cells over the past decades. My project will also contain the potential possibility of the use of innovative iron-binding drugs as novel anti-cancer therapeutics.