Nakagawara A
Division of Biochemistry, Chiba Cancer Center Research Institute.
Hum Cell. 1998 Sep;11(3):115-24.
Neuroblastoma is one of the most common pediatric solid tumors originating from the sympathoadrenal lineage of the neural crest. The tumors found in infants very frequently regress spontaneously by differentiating and/or undergoing programmed cell death, while those in children over one year of age are very aggressive and eventually kill the patients. The recent advances in neuroblastoma research have revealed that the neurotrophin signals, especially those through nerve growth factor and its receptor, TrkA, play an important role in regulating the regression of neuroblastoma. The genetic abnormalities such as allelic loss of the distal region of chromosome 1p, gain of chromosome 17q21-q25, and MYCN amplification, all of which are associated with the tumor aggressiveness, inhibit the regression of neuroblastoma. In the regressing tumor cells, caspases are induced and surviving, which is mapped to 17q25 and is overexpressed in the advanced stage tumors, is down-regulated. Thus, the molecular mechanism of spontaneous regression of neuroblastoma is now being unveiled. However, many more questions including the developmental machinery to trigger regression still remain to be clarified.
神经母细胞瘤是起源于神经嵴交感肾上腺谱系的最常见儿童实体瘤之一。在婴儿中发现的肿瘤经常通过分化和/或经历程序性细胞死亡而自发消退，而一岁以上儿童的肿瘤则具有很强的侵袭性，最终导致患者死亡。神经母细胞瘤研究的最新进展表明，神经营养因子信号，尤其是通过神经生长因子及其受体TrkA的信号，在调节神经母细胞瘤的消退中起重要作用。诸如1号染色体短臂远端区域的等位基因缺失、17号染色体q21-q25区域的扩增以及MYCN扩增等遗传异常，均与肿瘤侵袭性相关，会抑制神经母细胞瘤的消退。在消退的肿瘤细胞中，半胱天冬酶被诱导，而定位于17q25且在晚期肿瘤中过度表达的存活素则被下调。因此，神经母细胞瘤自发消退的分子机制正在被揭示。然而，包括触发消退的发育机制在内的更多问题仍有待阐明。
