Kogner P, Borgström P, Bjellerup P, Schilling F H, Refai E, Jonsson C, Dominici C, Wassberg E, Bihl H, Jacobsson H, Theodorsson E, Hassan M
Dept. of Woman and Child Health, Karolinska Institute, Karolinska Hospital, Stockholm, Sweden.
Eur J Cancer. 1997 Oct;33(12):2084-9. doi: 10.1016/s0959-8049(97)00212-8.
Neuroblastoma, a childhood tumour of the sympathetic nervous system, may in some cases differentiate to a benign ganglioneuroma or regress due to apoptosis. Somatostatin may inhibit neuroblastoma growth and induce apoptosis in vitro and was therefore investigated. Using a radioimmunoassay, we found that all ganglioneuromas contained high somatostatin concentrations (> 16 pmol/g), significantly higher than neuroblastomas (n = 117, median 2.8 pmol/g), healthy adrenals, Wilms' tumours, phaeochromocytomas and other neuroendocrine tumours (P < 0.001). Neuroblastomas contained more somatostatin than control tumours (P < 0.001-0.05). Neuroblastomas amplified for the MYCN oncogene contained less somatostatin than non-amplified tumours (1.2 pmol/g versus 4.0 pmol/g, respectively; P = 0.026). In a clinically unfavourable neuroblastoma subset (age > 12 months, stage 3 or 4) 16 children with high concentrations of somatostatin in primary tumours had a better prognosis than 23 with low somatostatin (46.7% versus 0% survival at 5 years, P < 0.005). Scintigraphy using 111In-pentetreotide identified tumours expressing high-affinity somatostatin receptors in vivo. However, no significant correlation was found between somatostatin receptor expression and peptide content in 15 tumours. Similarly, human SH-SY5Y neuroblastoma xenografts grown in nude rats showed low somatostatin concentrations, but were positive for somatostatin receptor scintigraphy. Treatment of these rats with the somatostatin analogue octreotide seemed to upregulate in vivo receptor expression of somatostatin and vasoactive intestinal peptide more effectively than 13-cis retinoic acid. In conclusion, somatostatin in neuroblastoma is associated with differentiation to benign ganglioneuromas in vivo and favourable outcome in advanced tumours. Furthermore, somatostatin receptor scintigraphy may identify tumours with high-affinity receptors in children that might benefit from targeted therapy using synthetic somatostatin analogues.
神经母细胞瘤是一种起源于交感神经系统的儿童肿瘤，在某些情况下可分化为良性神经节瘤或因凋亡而消退。生长抑素可能在体外抑制神经母细胞瘤的生长并诱导其凋亡，因此对其进行了研究。通过放射免疫分析，我们发现所有神经节瘤中生长抑素浓度都很高（>16 pmol/g），显著高于神经母细胞瘤（n = 117，中位数为2.8 pmol/g）、健康肾上腺、肾母细胞瘤、嗜铬细胞瘤及其他神经内分泌肿瘤（P < 0.001）。神经母细胞瘤中的生长抑素含量高于对照肿瘤（P < 0.001 - 0.05）。MYCN癌基因扩增的神经母细胞瘤中生长抑素含量低于未扩增的肿瘤（分别为1.2 pmol/g和4.0 pmol/g；P = 0.026）。在临床预后不良的神经母细胞瘤亚组（年龄>12个月，3期或4期）中，16例原发肿瘤生长抑素浓度高的儿童比23例生长抑素浓度低的儿童预后更好（5年生存率分别为46.7%和0%，P < 0.005）。使用111In-喷替酸奥曲肽进行闪烁扫描可在体内识别表达高亲和力生长抑素受体的肿瘤。然而，在15个肿瘤中未发现生长抑素受体表达与肽含量之间存在显著相关性。同样，在裸鼠体内生长的人SH-SY5Y神经母细胞瘤异种移植瘤生长抑素浓度较低，但生长抑素受体闪烁扫描呈阳性。用生长抑素类似物奥曲肽治疗这些大鼠似乎比13 - 顺式维甲酸更有效地在体内上调生长抑素和血管活性肠肽的受体表达。总之，神经母细胞瘤中的生长抑素与体内向良性神经节瘤的分化及晚期肿瘤的良好预后相关。此外，生长抑素受体闪烁扫描可识别儿童中具有高亲和力受体的肿瘤，这些肿瘤可能受益于使用合成生长抑素类似物的靶向治疗。
