Inhibition of tumor growth, vascularization, and collagenolysis in the rabbit cornea by medroxyprogesterone

Abstract

Medroxyprogesterone, dexamethasone, or cortisone, locally applied in sustained release polymer to rabbit V2 carcinoma implanted in the rabbit cornea, blocked neovascularization and three-dimensional growth of the tumor. These hormones similarly prevented the vascular proliferative response to implants in the rabbit cornea of mouse B-16 melanoma and also the response to implants of polymer containing tumor extract with angiogenesis activity. The inhibitory responses were accompanied by considerable reduction in collagenolytic activity released into culture medium by explants of the two tumors and of the corneal region containing angiogenic hepatoma extract. Morphologic studies revealed extensive three-dimensional disruption of the compact laminated collagenous structure of the corneal by untreated V2 carcinoma. In the presence of hormone the tumor grew slowly as a noninvasive two-dimensional plaque limited to the narrow region of the insertion pocket in the cornea, with no obvious disturbance of structure elsewhere. Cortisone was much less effective than medroxyprogesterone or dexamethasone. Testosterone and estradiol had no effect on the three measured properties. The data suggest that local hormonal interference with neovascularization, collagenase production, and tumor growth can prevent neoplastic invasion and destruction of a dense collagenous connective tissue.