Pietras A, Gisselsson D, Ora I, Noguera R, Beckman S, Navarro S, Påhlman S
Center for Molecular Pathology, Department of Laboratory Medicine, CREATE Health, Lund University, University Hospital MAS, Malmö, Sweden.
J Pathol. 2008 Mar;214(4):482-8. doi: 10.1002/path.2304.
High HIF-2alpha protein levels in the sympathetic nervous system-derived childhood tumour neuroblastoma as well as immature phenotype correlate to unfavourable outcome. Here we show that a small subset of perivascularly located, strongly HIF-2alpha-positive tumour cells (MYCN amplified) lacks expression of differentiation markers, but expresses neural crest and early sympathetic progenitor marker genes such as Notch-1, HES-1, c-Kit, dHAND, and vimentin. HIF-2alpha- and CD68-positive tumour-associated macrophages were frequently found close to the immature and HIF-2alpha-positive neuroblastoma cells and as VEGF levels are high in the perivascular niche, we hypothesize that neuroblastoma neural crest-like cells and macrophages cooperate to facilitate angiogenesis and thereby contribute to the aggressive neuroblastoma phenotype.
在源自交感神经系统的儿童肿瘤神经母细胞瘤中，高HIF-2α蛋白水平以及未成熟表型与不良预后相关。我们在此表明，一小部分位于血管周围、HIF-2α强阳性的肿瘤细胞（MYCN扩增）缺乏分化标志物的表达，但表达神经嵴和早期交感祖细胞标志物基因，如Notch-1、HES-1、c-Kit、dHAND和波形蛋白。经常在未成熟且HIF-2α阳性的神经母细胞瘤细胞附近发现HIF-2α和CD68阳性的肿瘤相关巨噬细胞，并且由于血管周围微环境中的VEGF水平较高，我们推测神经母细胞瘤神经嵴样细胞与巨噬细胞协同作用以促进血管生成，从而导致侵袭性神经母细胞瘤表型。
