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Involvement of heparan sulfate and related molecules in sequestration and growth promoting activity of fibroblast growth factor

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Abstract

Heparan sulfate proteoglycans (HSPGs) are ubiquitous macromolecules associated with the cell surface and extracellular matrix (ECM) of a wide range of cells of vertebrate and invertebrate tissues [1,2]. The basic HSPG structure consists of a protein core to which several linear heparan sulfate (HS) chains are covalently attached. The polysaccharide chains are typically composed of repeating hexuronic and D-glucosamine disaccharide units that are substituted to a varying extent with N- and O-linked sulfate moieties and N-linked acetyl groups [1,2]. Beside serving as a scaffold for the attachment of various ECM components (e.g., collagen, laminin, fibronectin), the binding of HS to certain proteins has been suggested to induce a conformational change which may lead to the exposure of novel reactive determinants or conversely stabilize an innert protein configuration [1–4]. Of particular significance is the interaction of HS with fibroblast growth factors (FGFs), mediating their sequestration, stabilization and high affinity receptor binding and signaling [3–7]. Cellular responses to FGFs may hence be modulated by metabolic inhibitors of HS synthesis and sulfation, HS-degrading enzymes, and synthetic mimetics of heparin/HS. In the present review we focus on the involvement of HS in basic FGF (bFGF) receptor binding and mitogenic activity and its modulation by species of heparin, HS, and synthetic polyanionic ‘heparin-mimicking’ compounds. The results are discussed in relation to the current thoughts on the dual involvement of low and high affinity receptor sites in the growth promoting and angiogenic activities of bFGF and other heparin-binding growth factors.

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Authors and Affiliations

  1. Department of Oncology, Hadassah-Hebrew University Hospital, Jerusalem, Israel

    Israel Vlodavsky, Hua-Quan Miao & Benjamin Medalion

  2. IBEX Technologies, Montreal, Canada

    Pamela Danagher

  3. Department of Biology, Technion, Israel Institute of Technology, Haifa, Israel

    Dina Ron

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  1. Israel Vlodavsky
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  2. Hua-Quan Miao
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  3. Benjamin Medalion
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  4. Pamela Danagher
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  5. Dina Ron
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Vlodavsky, I., Miao, HQ., Medalion, B. et al. Involvement of heparan sulfate and related molecules in sequestration and growth promoting activity of fibroblast growth factor. Cancer Metast Rev 15, 177–186 (1996). https://doi.org/10.1007/BF00437470

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