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The Involvement of Midkine, a Heparin-Binding Growth Factor, in Cancer Development

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Sugar Chains

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Abstract

Midkine is a secreted growth factor identified as a retinoic acid-induced gene in embryonal carcinoma cells. In terms of its molecular structure, a midkine consists of two domains, an N-terminal and a C-terminal domain. Previous reports have emphasized the significance of the C-terminal domain, which contains clusters of basic amino acids (clusters I and II). Cluster I is mainly responsible for the strong affinity of midkine to heparin. In addition to heparin, two other glycosaminoglycans, chondroitin sulfate and heparan sulfate, can also bind to midkine. The binding between cluster I in the C-terminal domain of midkine and glycosaminoglycans would mainly mediate the ligand-receptor interaction. Midkine is broadly expressed in various cancers and could have potential as both a tumor marker and prognostic factor. In neuroblastoma, the serum midkine level has been established as a reliable poor prognostic factor. Furthermore, it was recently revealed that midkine is physiologically involved in the tumorigenesis of neuroblastoma. Notch2 is likely to function as a receptor of midkine in neuroblastoma cells. Although anaplastic lymphoma kinase (ALK), another candidate receptor of midkine, was shown to be one of the predisposition genes of neuroblastoma, their ligand-receptor relationship in neuroblastoma has yet to be elucidated. Interestingly, it was reported that both Notch2 and ALK were glycosylated and that these glycosylations were necessary for their functions. Midkine could be an efficient molecular target in cancer therapy. Several molecular tools to target midkine have been developed, such as siRNA, antibodies, and RNA aptamers. Each of them exhibits certain therapeutic activities. Future investigation into the role of sugar chains in these activities would be of benefit. Progress in this and other matters pertaining to the clinical application of these molecular tools is eagerly anticipated.

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  1. Department of Biochemistry, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan

    Satoshi Kishida & Kenji Kadomatsu

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  1. Satoshi Kishida
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  2. Kenji Kadomatsu
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Correspondence to Satoshi Kishida .

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Editors and Affiliations

  1. Glycometabolome Team, Systems Glycobiology Research Group, RIKEN-Max-Planck Joint Research Center for Systems Chemical Biology, RIKEN Global Research Cluster, Wako, Saitama, Japan

    Tadashi Suzuki

  2. Department of Analytical Biochemistry, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan

    Kazuaki Ohtsubo

  3. Disease Glycomics Team, Systems Glycobiology Research Group, RIKEN-Max-Planck Joint Research Center for Systems Chemical Biology, RIKEN Global Research Cluster, Wako, Saitama, Japan

    Naoyuki Taniguchi

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Kishida, S., Kadomatsu, K. (2015). The Involvement of Midkine, a Heparin-Binding Growth Factor, in Cancer Development. In: Suzuki, T., Ohtsubo, K., Taniguchi, N. (eds) Sugar Chains. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55381-6_8

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