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 cornea 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 les 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.
Full text
PDF




Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Brem H., Folkman J. Inhibition of tumor angiogenesis mediated by cartilage. J Exp Med. 1975 Feb 1;141(2):427–439. doi: 10.1084/jem.141.2.427. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Eisenstein R., Goren S. B., Shumacher B., Choromokos E. The inhibition of corneal vascularization with aortic extracts in rabbits. Am J Ophthalmol. 1979 Dec;88(6):1005–1012. doi: 10.1016/0002-9394(79)90406-9. [DOI] [PubMed] [Google Scholar]
- Eisenstein R., Kuettner K. E., Neapolitan C., Soble L. W., Sorgente N. The resistance of certain tissues to invasion. III. Cartilage extracts inhibit the growth of fibroblasts and endothelial cells in culture. Am J Pathol. 1975 Nov;81(2):337–348. [PMC free article] [PubMed] [Google Scholar]
- Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med. 1971 Nov 18;285(21):1182–1186. doi: 10.1056/NEJM197111182852108. [DOI] [PubMed] [Google Scholar]
- Gimbrone M. A., Jr, Cotran R. S., Leapman S. B., Folkman J. Tumor growth and neovascularization: an experimental model using the rabbit cornea. J Natl Cancer Inst. 1974 Feb;52(2):413–427. doi: 10.1093/jnci/52.2.413. [DOI] [PubMed] [Google Scholar]
- Johnson-Wint B. A quantitative collagen film collagenase assay for large numbers of samples. Anal Biochem. 1980 May 1;104(1):175–181. doi: 10.1016/0003-2697(80)90295-x. [DOI] [PubMed] [Google Scholar]
- Johnson-Wint B. Regulation of stromal cell collagenase production in adult rabbit cornea: in vitro stimulation and inhibition by epithelial cell products. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5331–5335. doi: 10.1073/pnas.77.9.5331. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Langer R., Folkman J. Polymers for the sustained release of proteins and other macromolecules. Nature. 1976 Oct 28;263(5580):797–800. doi: 10.1038/263797a0. [DOI] [PubMed] [Google Scholar]
- Liotta L. A., Abe S., Robey P. G., Martin G. R. Preferential digestion of basement membrane collagen by an enzyme derived from a metastatic murine tumor. Proc Natl Acad Sci U S A. 1979 May;76(5):2268–2272. doi: 10.1073/pnas.76.5.2268. [DOI] [PMC free article] [PubMed] [Google Scholar]
- NAGAI Y., GROSS J., PIEZ K. A. DISC ELECTROPHORESIS OF COLLAGEN COMPONENTS. Ann N Y Acad Sci. 1964 Dec 28;121:494–500. doi: 10.1111/j.1749-6632.1964.tb14221.x. [DOI] [PubMed] [Google Scholar]
- Newsome D. A., Gross J. Regulation of corneal collagenase production: stimulation of serially passaged stromal cells by blood mononuclear cells. Cell. 1979 Apr;16(4):895–900. doi: 10.1016/0092-8674(79)90104-1. [DOI] [PubMed] [Google Scholar]
- Newsome N. A., Gross J. Prevention by medroxyprogesterone of perforation in the alkali-burned rabbit cornea: inhibition of collagenolytic activity. Invest Ophthalmol Vis Sci. 1977 Jan;16(1):21–31. [PubMed] [Google Scholar]
- Preis I., Langer R., Brem H., Folkman J. Inhibition of neovascularization by an extract derived from vitreous. Am J Ophthalmol. 1977 Sep;84(3):323–328. doi: 10.1016/0002-9394(77)90672-9. [DOI] [PubMed] [Google Scholar]
- Rhine W. D., Hsieh D. S., Langer R. Polymers for sustained macromolecule release: procedures to fabricate reproducible delivery systems and control release kinetics. J Pharm Sci. 1980 May;69(3):265–270. doi: 10.1002/jps.2600690305. [DOI] [PubMed] [Google Scholar]
- Shubik P., Feldman R., Garcia H., Warren B. A. Vascularization induced in the cheek pouch of the Syrian hamster by tumor and nontumor substances. J Natl Cancer Inst. 1976 Oct;57(4):769–774. doi: 10.1093/jnci/57.4.769. [DOI] [PubMed] [Google Scholar]
- Toole B. P., Biswas C., Gross J. Hyaluronate and invasiveness of the rabbit V2 carcinoma. Proc Natl Acad Sci U S A. 1979 Dec;76(12):6299–6303. doi: 10.1073/pnas.76.12.6299. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zetter B. R. Migration of capillary endothelial cells is stimulated by tumour-derived factors. Nature. 1980 May 1;285(5759):41–43. doi: 10.1038/285041a0. [DOI] [PubMed] [Google Scholar]