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Recombinant CD44-HABD is a novel and potent direct angiogenesis inhibitor enforcing endothelial cell-specific growth inhibition independently of hyaluronic acid binding

Abstract

CD44 is the main cellular receptor for hyaluronic acid (HA). We previously found that overexpression of CD44 inhibited tumor growth of mouse fibrosarcoma cells in mice. Here, we show that soluble recombinant CD44 HA-binding domain (CD44-HABD) acts directly onto endothelial cells by inhibiting endothelial cell proliferation in a cell-specific manner. Consequently, soluble recombinant CD44-HABD also blocked angiogenesis in vivo in chick and mouse, and thereby inhibited tumor growth of various origins at very low doses (0.25 mg/kg × day). The antiangiogenic effect of CD44 is independent of its HA-binding capacity, since mutants deficient in HA binding still maintain their antiangiogenic and antiproliferative properties. Recombinant CD44-HABD represents a novel class of angiogenesis inhibitors based on a cell-surface receptor.

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Acknowledgements

We thank Dr Anatoli Onischenko for the help with the chick CAM angiogenesis model. This work was supported by grants from the Swedish Cancer Society, the Estonian Science Foundation (3841, 5129) and Howard Hughes Medical Institute's International Research Fellowship. PK is an International Senior Research Fellow of the Wellcome Trust.

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Correspondence to Priit Kogerman.

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Päll, T., Gad, A., Kasak, L. et al. Recombinant CD44-HABD is a novel and potent direct angiogenesis inhibitor enforcing endothelial cell-specific growth inhibition independently of hyaluronic acid binding. Oncogene 23, 7874–7881 (2004). https://doi.org/10.1038/sj.onc.1208083

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