Cancer Biology Group, Department of Pharmacy, Health and Well Being, Cancer Biology and Therapeutics, Faculty of Applied Sciences, University of Sunderland Sunderland, UK ; Children's Cancer Institute, University of New South Wales Sydney, NSW, Australia.
Cancer Biology Group, Department of Pharmacy, Health and Well Being, Cancer Biology and Therapeutics, Faculty of Applied Sciences, University of Sunderland Sunderland, UK.
Front Cell Dev Biol. 2015 Dec 2;3:77. doi: 10.3389/fcell.2015.00077. eCollection 2015.
The prognostic value of cancer stem cell markers in various cancer subtypes is a well documented research area. Our findings show that the stem cell marker Lgr5 is associated with an aggressive phenotype in neuroblastoma. Here, we discuss these findings within the context of recent studies in several cancers such as lung, colorectal and intestinal cancer, glioblastoma and ewing's sarcoma. Neuroblastoma continues to be an elusive disease, due to its heterogeneous presentation ranging from spontaneous regression to aggressive metastatic disease and intertwined genetic variability. Currently, the most significant prognostic marker of high risk disease and poor prognosis is amplification of the MYCN oncogene, which is found in approximately 25% of cases (Huang and Weiss, 2013). With this in mind, there is still much to learn about the driving mechanisms of this aggressive pediatric tumor. Neuroblastoma development is thought to be the result of aberrant differentiation of the cell of origin, embryonic neural crest cells which then migrate and invade during the developmental stage (Joshi et al., 2007). Aberrant cells are those which would, under normal conditions form the mature tissues of the sympathetic ganglia and adrenal medulla. Tumors are known to develop indiscriminately along the radius of the sympathetic ganglia, although it is well established that the adrenal glands are fundamentally the most common primary site (Jessen and Mirsky, 2005).
癌症干细胞标志物在各种癌症亚型中的预后价值是一个有据可查的研究领域。我们的研究结果表明,干细胞标志物 Lgr5 与神经母细胞瘤中的侵袭表型有关。在这里,我们将这些发现置于肺癌、结直肠癌和肠癌、胶质母细胞瘤和尤文肉瘤等几种癌症的最新研究背景下进行讨论。由于其表现形式多样,从自发性消退到侵袭性转移性疾病,以及交织的遗传变异性,神经母细胞瘤仍然是一种难以捉摸的疾病。目前,高危疾病和预后不良的最重要预后标志物是 MYCN 癌基因的扩增,大约 25%的病例中发现了这种基因扩增(Huang 和 Weiss,2013)。考虑到这一点,人们仍然需要了解这种侵袭性儿科肿瘤的驱动机制。神经母细胞瘤的发展被认为是起源细胞(胚胎神经嵴细胞)异常分化的结果,这些细胞随后在发育阶段迁移和侵袭(Joshi 等人,2007)。异常细胞是指在正常情况下会形成交感神经节和肾上腺髓质成熟组织的细胞。肿瘤被认为是沿着交感神经节的半径无差别地发展的,尽管已经确立的是,肾上腺是最常见的主要部位(Jessen 和 Mirsky,2005)。