The role of hyaluronan in tumour neovascularization (review)

Tumour growth and metastasis are totally dependant upon neovascularization. The target cell for tumour neovascularization is the blood‐vessel endothelial cell, and specific angiogenic molecules produced or induced by the tumour are believed to initiate the process. In this report, we review one of these angiogenic molecules, the glycosaminoglycan hyaluronan (HA), which appears to have differing roles in neovascularization depending on its molecular mass. High‐molecular‐mass HA is anti‐angiogenic whereas oligosaccharides of HA, of specific size, actively stimulate endothelial‐cell proliferation and migration, 2 of the key events associated with neovascularization, and induce angiogenesis in vivo. We provide details of the action of HA oligosaccharides on endothelial cells, from binding to cell‐surface receptors, through activation of signal transduction pathways and gene expression to protein synthesis, cell proliferation and cell migration. We also suggest a model to account for HA of differing molecular mass being present, at different locations, within a single tumour and how this HA aids both general tumour growth and tumour metastasis.