Neurotrophic factor expression in childhood low-grade astrocytomas and ependymomas.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Chiaretti
Antonio
A
Paediatric Intensive Care Unit, Catholic University of Sacred Heart, 00168 Rome, Italy. achiaretti@yahoo.it
Aloe
Luigi
L
Antonelli
Alessia
A
Ruggiero
Antonio
A
Piastra
Marco
M
Riccardi
Riccardo
R
Tamburrini
Giampiero
G
Di Rocco
Concezio
C
D000293:Adolescent; D001254:Astrocytoma / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D004806:Ependymoma / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006801:Humans; D007124:Immunoenzyme Techniques / Q000379:methods; D007150:Immunohistochemistry / Q000379:methods; D007223:Infant; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D020800:Receptor, Nerve Growth Factor / Q000378:metabolism; D020917:Receptor, trkA; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D019208:Brain-Derived Neurotrophic Factor; D002352:Carrier Proteins; C495039:GDNF protein, human; D051100:Glial Cell Line-Derived Neurotrophic Factor; D008565:Membrane Proteins; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D020800:Receptor, Nerve Growth Factor; D020917:Receptor, trkA