SERUM CONCENTRATIONS OF INSULIN-LIKE GROW TH-FACTORS (IGF)-I AND IGF-II AND OF IGF BINDING-PROTEINS (IGFBP)-2 AND IGFBP-3 IN 49 CHILDREN WITH ALL, NHL OR SOLID TUMORS

The IGF regulatory system has been shown to mediate mitogenic effects during normal growth and tumor proliferation. The bioavailability of b oth IGF-I and IGF-II is regulated by at least six specific IGF binding proteins (IGFBPs). Whereas IGFBP-3 is the main IGFBP postnatally, IGF BP-2 is the predominant IGFBP during fetal life. In addition, IGFBP-2 is expressed in a range of tumor cell lines. In order to investigate t he IGF regulatory pathway in malignancies we analyzed by RIA serum sam ples of 49 children with leukemia, Non-Hodgkins' Lymphoma (NHL) or sol id tumors at the time of diagnosis. Serum concentrations of IGF-I (mea n/range: - 2.4/0.3 to -9.9 SDS), IGF-II (-2.5/0.2 to -5.6 SDS) and IGF BP-3 (-1.3/2.2 to -6.8 SDS) were significantly decreased, but IGFBP-2 (3.2/-0.9 to 8.6 SDS) was elevated. Both absolute as well as SDS value s of IGF-I, -II and the sum of IGF-I and IGF-II (r = -0.49, p < 0.01) were inversely correlated with IGFBP-2. Serum levels of the growth fac tors IGF-I and IGF-II were significantly decreased in different types of malignancies to concentrations usually seen only in patients with g rowth hormone deficiency or during starvation. However, the elevated l evels of IGFBP-2 in 70% of our patients exceeded by far those in growt h hormone deficiency. Furthermore, in this study we could demonstrate that serum levels of IGF-I and IGF-II were inversely correlated to IGF BP-2 independent on the type of malignancy, indicating a common regula tory mechanism of the IGF signaling pathway in these diseases.