Chiaretti Antonio, Aloe Luigi, Antonelli Alessia, Ruggiero Antonio, Piastra Marco, Riccardi Riccardo, Tamburrini Giampiero, Di Rocco Concezio
Paediatric Intensive Care Unit, Catholic University of Sacred Heart, 00168 Rome, Italy.
Childs Nerv Syst. 2004 Jun;20(6):412-9. doi: 10.1007/s00381-004-0959-6. Epub 2004 May 6.
Neurotrophic factors (nerve growth factor [NGF], brain-derived neurotrophic factor [BDNF] and glial-derived neurotrophic factor [GDNF]) are growth factors implicated in the growth and differentiation of brain nerve cells. An involvement of these factors in the biology and progression of some specific tumours has been suggested. In accordance with the role of neurotrophic factors in tumour behaviour the aim of the present study was to investigate their expression in two childhood brain neoplasms, namely low-grade astrocytomas and ependymomas.
We investigated the NGF, BDNF, GDNF and NGF receptors (TrkA and p75) expression in the tumour tissues, cerebrospinal fluid (CSF) and plasma of ten children affected by low-grade astrocytomas and ependymomas. Control tissue samples (together with CSF and plasma samples) were obtained from patients who underwent surgery for cerebral vascular or epileptogenic lesions.
The expression of NGF decreases both in tumour samples and in the CSF of affected children compared with controls. BDNF instead increases in CSF, while the expression of GDNF remains unchanged both in tissues and in CSF. No differences were found in neurotrophic factor plasma levels in patients or in controls. Gene expression of NGF and its high-affinity receptor (TrkA) are reduced in tumour tissues, whereas the number of cells immunopositive to the low-affinity NGF receptor (p75) is increased.
Reduced expression of NGF and TrkA has been shown in low-grade astrocytomas and ependymomas. These findings may be related to the role of this neurotrophin in cell differentiation and apoptosis. The different expression of NGF, BDNF, and GDNF in low-grade astrocytomas and ependymomas suggests that a different degree of redundancy exists among members of the neurotrophic factor family and that their expression may be correlated with the biology and the behaviour of these tumours.
神经营养因子(神经生长因子[NGF]、脑源性神经营养因子[BDNF]和胶质细胞源性神经营养因子[GDNF])是与脑神经细胞生长和分化相关的生长因子。有人提出这些因子参与了某些特定肿瘤的生物学过程和进展。根据神经营养因子在肿瘤行为中的作用,本研究的目的是调查它们在两种儿童脑肿瘤,即低级别星形细胞瘤和室管膜瘤中的表达情况。
我们调查了10例患有低级别星形细胞瘤和室管膜瘤的儿童的肿瘤组织、脑脊液(CSF)和血浆中NGF、BDNF、GDNF及NGF受体(TrkA和p75)的表达情况。对照组织样本(连同CSF和血浆样本)取自接受脑血管或致痫性病变手术的患者。
与对照组相比,NGF在肿瘤样本和患病儿童的CSF中的表达均降低。而BDNF在CSF中增加,GDNF在组织和CSF中的表达均保持不变。患者和对照组的神经营养因子血浆水平未发现差异。肿瘤组织中NGF及其高亲和力受体(TrkA)的基因表达降低,而对低亲和力NGF受体(p75)免疫阳性的细胞数量增加。
已证实在低级别星形细胞瘤和室管膜瘤中NGF和TrkA表达降低。这些发现可能与这种神经营养蛋白在细胞分化和凋亡中的作用有关。低级别星形细胞瘤和室管膜瘤中NGF、BDNF和GDNF的不同表达表明神经营养因子家族成员之间存在不同程度的冗余,并且它们的表达可能与这些肿瘤的生物学特性和行为相关。