Insulin-like growth factor-binding protein-2 concentrations in cerebrospinal fluid and serum of children with malignant solid tumors or acute leukemia.
Many tumor cell lines express insulin-like growth factors (IGFs) as autocrine growth factors and IGF-binding protein-2 (IGFBP-2) as a major IGFBP, which, in turn, regulates the bioavailability and bioactivity of IGFs. The aim of our study was to investigate 1) whether children with malignancies have elevated IGFBP-2 levels in cerebrospinal fluid (CSF) and serum, and 2) whether IGFBP-2 levels in these biological fluids could be useful markers for the diagnosis and follow-up of certain tumor types. We, therefore, measured IGFBP-2 levels in the CSF and serum of children with malignancies by Western ligand blot analysis; RIA with alpha IGFBP-2, a polyclonal antibody for human IGFBP-2; and immunoprecipitation with alpha IGFBP-2 and alpha Hec-1a, a polyclonal antibody that recognizes IGFBP-2 and -3. Furthermore, the expression of IGFBP-2 messenger ribonucleic acid in tumor tissue from three central nervous system (CNS) tumor patients was analyzed by Northern blot analysis. We examined CSF from 21 children with malignant CNS tumors, 25 patients with acute leukemia, and 4 patients with peripheral solid tumors and compared the IGFBP-2 levels with those in CSF from 21 patients who received a lumbar puncture to exclude meningitis. Serum was obtained from 7 patients with solid tumor, 12 patients with malignant CNS tumor, and 16 patients with acute leukemia. The serum IGFBP-2 levels were compared to serum levels in 5 patients with sarcoma who had reached complete remission and 13 normal control children. CSF and serum were collected at the same time, before initiation of therapy. Patients with malignant CNS tumors showed elevated IGFBP-2 levels in CSF (P < 0.001), whereas patients with solid peripheral tumor or acute leukemia had normal IGFBP-2 levels in CSF. CNS tumor patients with microscopically detectable malignant cells in the CSF had the highest CSF IGFBP-2 levels. Serum IGFBP-2 levels were increased in patients with solid peripheral tumors (P < 0.05), whereas patients in complete remission had normal serum IGFBP-2 levels. In summary, IGFBP-2 was elevated specifically in CSF from patients with CNS tumor, whereas IGFBP-2 serum levels were elevated in children with various peripheral tumors. We conclude that IGFBP-2 in CSF could be a specific marker for malignant CNS tumors. We detected high IGFBP-2 messenger ribonucleic acid expression in 1 of 3 CNS tumor tissues analyzed.
Müller
H L
HL
Department of Pediatrics, Stanford University School of Medicine, California 94305.
Oh
Y
Y
Lehrnbecher
T
T
Blum
W F
WF
Rosenfeld
R G
RG
D000293:Adolescent; D015152:Blotting, Northern; D015153:Blotting, Western; D002352:Carrier Proteins / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000235:genetics; D016543:Central Nervous System Neoplasms / Q000378:metabolism* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007163:Immunosorbent Techniques; D007223:Infant; D018971:Insulin-Like Growth Factor Binding Protein 2; D007938:Leukemia / Q000378:metabolism*; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism; D008297:Male; D008527:Medulloblastoma / Q000378:metabolism / Q000473:pathology; D008581:Meningitis / Q000134:cerebrospinal fluid; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis
D002352:Carrier Proteins; D018971:Insulin-Like Growth Factor Binding Protein 2; D012333:RNA, Messenger