Tumor growth can be separated into an avascular phase and a vascular phase. During the avascular phase tumor growth is supported by simple diffusion, which is only sufficient when tumors are only a few milimeters in diameter. Once tumors reach a size where diffusion is no longer adequate to sustain their growth, host blood vessels are needed in order to penetrate the tumor mass and initiate further growth. From this dependency of tumor growth on neovascularization it is inferred that blockage of tumor angiogenesis might be used in cancer therapy, causing tumors to remain at a small size and leaving tumor cells in a dormant state. A promising candidate for such an anti-angiogenic therapy has been identified by our laboratory within the low-molecular-ultrafiltrates of hyaline cartilage and urinary bladder extracts. It is a non-toxic growth inhibitor of vascular endothelial cells in culture and an inhibitor of tumor angiogenesis in the rabbit corneal assay. To obtain sufficient quantities of pure endothelial cell growth inhibitor for experimental therapy, it is proposed in this application that the inhibitor is prepared by immunoadsorption to its monoclonal antobody. With hybridoma technology, such an antibody can be raised using as an antigen a chromatographic subfraction of the cartilage or bladder ultrafiltrate that contains the endothelial cell growth inhibitor. This procedure has the distinct advantage that loss of active material, inherent to most biochemical purification procedures used in the past, can be reduced to an absolute minimum. The purified endothelial cell growth inhibitor will be tested for (1) effect on endothelial cell growth and cell cycle; (2) inhibition of endothelial cell migration (chemotaxis); (3) effect on proteinase synthesis of stimulated endothelial cell and (4) efficiency in inhibiting tumor angiogenesis in the rabbit corneal assay and tumor growth and metastasis in animal tumors.
| Pauli, B U; Kellen, J A; Ng, R (1987) Correlation of fibrinolytic activity with invasion and metastasis of R3230 AC rat mammary carcinoma cell lines. Invasion Metastasis 7:158-71 |
