Inhibition of angiogenesis by anthracyclines and titanocene dichloride.

The anthracycline antibiotics, daunorubicin, doxorubicin, and epirubicin, which are widely used for treatment of malignancies, have been evaluated for their effect on angiogenesis in relation to the inhibition of collagenase type IV reported previously. In the chick chorioallantoic membrane (CAM) system of angiogenesis, anthracyclines inhibited vascular density at doses of 5-20 micrograms/disc as well as collagenous protein biosynthesis, which is a reliable index of angiogenesis. Similarly, all three anthracyclines inhibited tube formation in the in vitro system of angiogenesis using human umbilical vein endothelial cells (HUVECs) plated on Matrigel.

Suppression of angiogenesis by the antitumor agent titanocene dichloride.

Titanocene dichloride, which is an active antitumor agent against solid but not blood-borne tumors, suppresses angiogenesis and inhibits biosynthesis of collagenous proteins in the in vivo system of the chorioallantoic membrane of the chick embryo. The agent does not affect total protein biosynthesis in the same system. At non-toxic dose regimens titanocene dichloride retards the growth of Walker 256 carcinosarcoma transplants in rats and reduces the number of seeded implants in the mesenteric bed.

Basement membrane biosynthesis as a target for developing inhibitors of angiogenesis with anti-tumor properties.

Basement membrane (BM) exerts profound influence on endothelial cell (EC) behavior. In addition BM is a structural element of blood vessels; in fact at some point of their formation blood vessels are bare EC tubes lined with the BM produced by these EC. We thought, therefore, that a quantitative relationship must exist between the rate of BM synthesis and angiogenesis, and that interfering with BM synthesis must have an effect on angiogenesis.

Endothelial injury causes degradation of adjacent basement membranes and promotes their invasion by A549 carcinoma cells.

Experiments in vivo have demonstrated that endothelial cell injury promotes the local arrest of circulating, intravascular cancer cells and the subsequent formation of metastatic tumors. The experiments described here were performed to test the hypothesis that injury of the endothelium also causes damage to the adjacent vascular basement membrane, which in turn facilitates the passage of cancer cells across the vessel wall. Confluent monolayers of bovine pulmonary artery endothelial cells were incubated with 3H-2-deoxyglucose or 3H-proline to label the endothelial cells or the basement membrane, respectively.

Effect of divalent metal ions on collagenase from Clostridium histolyticum.

The collagenase from Clostridium histolyticum (EC 3.4.24.