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.

The molecular mass of hyaluronic acid (HA) rather than its serum concentration alone may be a hallmark of certain types of malignancy. A radiometric assay was used to measure HA levels in 35 children with renal tumours [33 Wilms' tumours and 2 bone metastasizing renal tumours of childhood (BMRTC)] and 20 normal siblings of children with cancer. The HA level in the sera of normal children was barely detectable and had a molecular mass of 1-5 x 10(5). In both Wilms' and BMRTC patients, very high levels of HA were found in preoperative serum samples; these fell dramatically following surgical excision of the tumours. A novel finding of our study was the presence of low-molecular-mass HA (similar to the angiogenic fragments of HA) in the sera of BMRTC patients. In contrast, high-molecular-mass HA (which is not angiogenic) was found in the sera of Wilms' patients (2 x 10(6) kDa). Following surgery in BMRTC patients, not only did serum HA levels fall to a value within normal ranges, but also the HA which remained was of high molecular mass.

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The serum hyaluronan (HA) level of 238 women with breast cancer was measured by means of a specific radiometric assay. The results show no significant increase in serum HA when compared to levels in 120 control sera. A number of prognostic factors were evaluated including stage of disease, lymph-node involvement, tumour size, histology and presence of oestrogen and progesterone receptors in the tumour. No correlation was found with serum HA concentration and we conclude that serum HA level is of no prognostic significance in breast cancer.