Abstract
LAM S5 is a polysulphated derivative of the glucan laminarian that inhibits basic fibroblast growth factor (bFGF) binding and the bFGF-stimulated proliferation of fetal bovine heart endothelial (FBHE) cells. This report demonstrates that LAM S5 has anti-angiogenic activity, as shown by inhibition of tubule formation by endothelial cells cultured on Matrigel and inhibition of vascularisation of the chick chorioallantoic membrane. In addition, LAM S5 caused a tumour growth delay of the murine RIF-1 tumour of 2.6 days (P = 0.01).
Highlights
At least some of the anti-tumour activities of these compounds can be attributed to inhibition of heparin-binding angiogenic growth factors produced by tumour cells (Zugmaier et al, 1992; Nakayama et al, 1993)
We have recently identified a highly sulphated derivative of the /3-1,3glucan laminarin, designated LAM S5, which inhibits basic fibroblast growth factor binding and the bFGF-stimulated proliferation of fetal bovine heart endothelial (FBHE) cells (Hoffman et al, 1995a). bFGF is a potent angiogenic factor and is present at elevated levels in the urine of some cancer patients (Nguyen et al, 1994)
In this study we have evaluated the anti-angiogenic and anti-tumour activities of LAM S5
Summary
'Clinical Oncology and Radiotherapeutics Unit, MRC Centre, Hills Road, Cambridge CB2 2QH, UK; 2Department of Pharmacy, University of Regensburg, 93040 Regensburg, Germany. Summary LAM S5 is a polysulphated derivative of the glucan laminarin that inhibits basic fibroblast growth factor (bFGF) binding and the bFGF-stimulated proliferation of fetal bovine heart endothelial (FBHE) cells. Inhibition of tumour neovascularisation, or angiogenesis, is a promising new strategy for the treatment of cancer (see Scott and Harris, 1994 for recent review) Several polysulphated carbohydrates, such as pentosan polysulphate (PPS), chitin derivatives and the bacteria-derived DS-4152, are antiangiogenic and inhibit tumour growth in animal models (Zugmaier et al, 1992; Murata et al, 1991; Tanaka et al, 1989). We have recently identified a highly sulphated derivative of the /3-1,3glucan laminarin, designated LAM S5 (molecular weight 12 kDa), which inhibits basic fibroblast growth factor (bFGF) binding and the bFGF-stimulated proliferation of fetal bovine heart endothelial (FBHE) cells (Hoffman et al, 1995a). In this study we have evaluated the anti-angiogenic and anti-tumour activities of LAM S5
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