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Glycosaminoglycan‐binding cytokines as tumor markers

A significant proportion of cytokines bind to glycosaminoglycans such as heparin. Glycosaminoglycans are involved in signaling, stabilization and/or storage of these cytokines. Typical examples of glycosaminoglycan‐binding cytokines are basic fibroblast growth factor (bFGF), interleukin‐8 (IL‐8), monocyte chemoattractant protein‐1 (MCP‐1), vascular endothelial growth factor (VEGF), VEGF‐C, hepatocyte growth factor (HGF), granulocyte colony‐stimulating factor (G‐CSF), midkine, and pleiotrophin. All are present in the tumor microenvironment and promote tumor growth, tumor invasion and/or tumor angiogenesis. Serum or plasma levels of glycosaminoglycan‐binding cytokines are frequently elevated in patients with various malignant tumors. High levels of these cytokines are usually correlated with the occurrence of metastasis and a poor prognosis. The mode of elevation of individual glycosaminoglycan‐binding cytokines in patients with malignant tumors is summarized here. Further studies, especially with multiple cytokines, are expected to make assays clinically useful for both early detection and prognostic prediction.