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.