Hoehner J C, Olsen L, Sandstedt B, Kaplan D R, Påhlman S
Department of Pathology, Uppsala University Hospital, Sweden.
Am J Pathol. 1995 Jul;147(1):102-13.
Interactions of the trk family of tyrosine kinase receptors with neurotrophins result in growth and maturational changes in neuronal cells. The continued progression, maturation, or regression of neuroblastoma, an embryonal, sympathetic nervous system-derived tumor of infants and children, might be governed by neurotrophic influences. Immunocytochemistry was utilized to evaluate TrkA, TrkB, and TrkC protein expression at the cellular level in the developing human fetal sympathetic nervous system and in a selection of neuroblastoma tumor specimens. TrkA and TrkC expression was identified in sympathetic ganglia and within the adrenal medulla, with intense TrkB expression restricted to paraganglia, of the normal developing human sympathetic nervous system. In neuroblastoma, pp140trkA expression correlated positively with favorable tumor stage (P = 0.0027) and favorable outcome (P = 0.026). No statistically significant correlation of TrkC expression with outcome was evident; however, both TrkA and TrkC expression was most apparent in tumor cells of increased differentiation. TrkB expression was primarily localized to cells within the fibrovascular tumor stroma. A model of neurotrophin receptor expression and neurotrophin reactivity with differentiation is proposed. The existence and spatial distribution of neurotrophin receptors in neuroblastoma lend supportive evidence that neurotrophic influences may be involved in tumor persistence or regression.
酪氨酸激酶受体trk家族与神经营养因子的相互作用导致神经元细胞的生长和成熟变化。神经母细胞瘤是一种起源于胚胎、交感神经系统的婴幼儿肿瘤，其持续进展、成熟或消退可能受神经营养影响的支配。利用免疫细胞化学方法，在发育中的人类胎儿交感神经系统和一系列神经母细胞瘤肿瘤标本中，从细胞水平评估TrkA、TrkB和TrkC蛋白的表达。在正常发育的人类交感神经系统中，TrkA和TrkC表达见于交感神经节和肾上腺髓质内，而强烈的TrkB表达仅限于副神经节。在神经母细胞瘤中，pp140trkA表达与良好的肿瘤分期（P = 0.0027）和良好的预后（P = 0.026）呈正相关。TrkC表达与预后无明显统计学相关性；然而，TrkA和TrkC表达在分化增加的肿瘤细胞中最为明显。TrkB表达主要定位于纤维血管肿瘤基质内的细胞。提出了一个神经营养因子受体表达及神经营养因子与分化反应性的模型。神经母细胞瘤中神经营养因子受体的存在和空间分布提供了支持性证据，表明神经营养影响可能参与肿瘤的持续存在或消退。
