A possible role for spontaneous interleukin‐8 production by acute myeloid leukemic cells in angiogenesis related processes: Work in progress

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Abstract
Background Recently, the role of inter‐leukin‐8 (IL‐8) in angiogenesis was reported. We consequently addressed here the question whether IL‐8 produced by acute myeloid leukemia (AML) blasts might have a comparable function. Procedure In 21 pediatric patients with AML the role of AML derived IL‐8 in angiogenesis related processes were investigated. Therefore, IL‐8 protein and mRNA expression were measured and endothelial cell (EC) migration and proliferation assays were performed. In addition, bFGF and VEGF mRNA expression were measured by RT‐PCR. Results In the supernatant of the AML blasts, IL‐8 protein was present in a varying amount (median 0.86 μgL, range: 0.1–320 μg/L) and confirmed by RT–PCR. Normal bone marrow mononuclear cells secreted a significant lower amount of IL‐8 protein (median: 0.053 μg/L, range: 0.023–0.055 μg/L, P = 0.007).Seven of the 17 tested AML supernatants induced a varying low amount of EC proliferation compared to control media, which was not inhibited by anti‐IL‐8 antibodies. In contrast, in the EC migration assay, 15 out of the 17 AML supernatants tested, showed an increased EC migration (median fold increase: 1.97, range: 0.66–6.36, P = 0.002) compared to control medium. The increase in EC migration could partially be blocked by anti‐IL‐8 in 59% of the cases (18% decrease, range 0–62%, P = 0.003). Other contributors for the increase in EC migration were also determined. Vascular endothelial growth factor (VEGF) transcripts by RT‐PCR were demonstrated in six out of the nine tested AML cases, while no transcripts for basic fibroblast growth factor (VEGF) could be shown. Conclusions Neutralizing anti IL‐8 antibodies inhibit EC migration when stimulated with AML supernatant. This suggests a facilitating role for AML‐derived IL‐8 in an important step in angiogenesis. Med Pediatr Oncol 2001;37:511–517.