| abstract |
CD44 is a receptor for hyaluronic acid and has complex actions in cell functional physiology, cell migration and tumor metastasis. We have previously found that overexpression of human CD44 receptor in mouse fibrosarcoma cells inhibits subcutaneous tumor growth in mice [Kogerman et al., Oncogene 1997; 15: 1407-16; Kogerman et al., Clin Exp Metastasis 1998; 16: 83-93]. Here it is proved that the tumor growth inhibitory effect of CD44 is caused by the prevention of angiogenesis. In addition, the inventors have found that soluble recombinant CD44 hyaluronic acid binding domain (CD44HABD) inhibits in vivo angiogenesis in chickens and mice, thereby preventing human tumor growth of various origins. The anti-angiogenic effect of CD44-HABD is independent of hyaluronic acid (HA) binding. This is because the non-HA binding variants of CD44HABD still maintain anti-angiogenic properties. The present invention discloses soluble CD44 recombinant proteins as a new class of angiogenesis inhibitors based on targeting of vascular cell surface receptors. Disclosed are methods of inhibiting angiogenesis and treating human tumors using recombinant CD44 proteins and analogs thereof. As a further embodiment of the invention, screening methods for new drug targets using CD44 recombinant proteins and their analogs are described. |