Neuroblastoma aggressiveness in relation to sympathetic neuronal differentiation stage

Abstract

Neuroblastoma aggressiveness in relation to sympathetic neuronal differentiation stage.Mohlin, Sofie; Wigerup, Caroline; Påhlman, Sven Link to publication Citation for published version (APA): Mohlin, S., Wigerup, C., & Påhlman, S. (2011). Neuroblastoma aggressiveness in relation to sympathetic neuronal differentiation stage. Seminars in Cancer Biology, 21(4), 276-282. DOI: 10.1016276-282. DOI: 10. /j.semcancer.2011 General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal Neural crest and development of the sympathetic nervous systemThe sympathetic nervous system (SNS) originates from the neural crest, an ephemeral structure during vertebrate development. Located along the neural fold, cells on the neural tube in the ectoderm give rise to the neural crest, in turn generating different derivatives, such as the cranial, hindbrain, vagal and trunk neural crest (reviewed in (9)). Trunk neural crest cells migrate from the neural tube along two defined routes, with one group of cells migrating early along a ventral pathway, giving rise to glial cells and neurons, whereas a later migrating group of cells follows a lateral pathway and gives rise to melanocytes in the skin (10, 11). These mutations were rare in all four studies indicating locus heterogeneity for predisposition of inherited disease, but still demonstrated the importance of the PHOX2B gene in neuroblastoma oncogenesis and initiation (Fig. 1) (58), and Fig. 1). Neuroblastoma differentiation stage and clinical outcomeThere is a well-documented difference in aggressive behavior between the morphologically undifferentiated (neuroblastoma proper) and the differentiated (ganglioneuroblastoma, Cellular adaptation to hypoxiaThe biological consequences of hypoxia involve induced angiogenesis, a switch in glucose metabolism and increased invasion and migration capacities, changes that stimulate tumor progression. The hypoxic response is mainly mediated by stabilization of the hypoxia inducible factor (HIF) proteins. HIFs are heterodimeric transcription factors composed of an oxygen sensitive  subunit and a constitutively expressed  subunit. At physiological oxygen levels, the  subunit is hydroxylated by the oxygen-dependent prolyl hydroxylases (PHDs), leading to interaction with the von Hippel Lindau-ubiquitin ligase complex, followed by ubiquitination and proteasomal degradation. At hypoxia, the PHDs are inactive leading to the 9 stabilization of the HIF- subunits, and by dimerization with the  subunit the comple...

Ultrastructural morphometry of neurosecretory granules in the neuroblastomas of paediatric patients

“…Present ultrastructural findings support previous findings that cells in tumours with an unfavorable prognosis appear less differentiated (2). Our finding of the NSGs in cell bodies could, therefore, imply that NSGs have not yet extended from cell bodies into cell processes.…”

“…Peripheral neuroblastic tumours display a correlation between their morphological characteristics and prognoses, which could imply that systematic investigation of these differences between tumour cells, with varying outcomes and levels of differentiation, could prove to be useful in revealing the mechanisms of biological development of the said tumours (2).…”

“…the organ of Zuckerkandl) (1). Carcinogenesis initiates in the fetal or early neonatal period, disabling further differentiation of cells of the future adrenal medulla, autonomic nervous system, Schwann cells, melanocytes and some members of the diffuse neuroendocrine system (DNES) (2). These tumours represent a type of the most frequently diagnosed solid, extracranial growths of early childhood and additionally stand out by the heterogeneous wide scope of clinical symptoms their diagnosis entails (1).…”

Neuroblastoma cells injected into experimental mature teratoma reveal a tropism for embryonic loose mesenchyme

“…A homing to the perivascular niche is in line with the notion that NB could be considered a stem cell disease of the sympathetic nervous system (5) and that the perivascular niche supports stem cell self-renewal capacity and an undifferentiated state of neural tumor cells (22).…”

“…Neuroblastoma is a small round cell tumor of childhood and is considered to arise from dedifferentiation of primordial neural crest cells that populate the sympathetic trunks and the adrenal medulla (reviewed in ref. 5). During this process, an aberrant response to microenvironment cues may play an important role in modulating the tumor phenotype, and hence also lead to the variable clinical presentations of NB in patients.…”