Age is the single greatest risk factor for the development of cancer. A reduction in host surveillance, longer exposure to carcinogens, and accumulation of mutations may all contribute to age-associated cancers. However, adequate animal models to study these processes have not been available. We have developed improved methods to grow lines of human prostate cells as tumors. Lines of breast tumor cells arising spontaneously in aged female rats also have been developed. We also have developed a simple, quantitative assay to measure vascularization and assess angiogenic and potential anti-angiogenic factors. These systems provide the opportunity to investigate the genetic events underlying the development of these cancers and explore various methods of cancer prevention. Although the incidence of cancer increases with age, tumors of the prostate, breast, and ovary grow more slowly and progression is less aggressive in the elderly. Several mouse tumor models are being used to identify factors which may contribute to inhibition of tumor growth in aged animals. These factors are being tested in human prostate and rat breast tumor models in an effort to identify the source(s) of tumor growth inhibition with age. Programmed cell death (apoptosis) may be involved in age-dependent degeneration. Endothelial cell apoptosis occurs when cells are undergoing differentiation on Matrigel (an extract of basement membrane proteins) and when trophic factors are withdrawn. Matrigel prepared from old animals is especially potent at inducing apoptosis of endothelial cells. These protein preparations may be a useful source of negative regulators (from old hosts) or trophic factors (from young hosts) which may influence not only vascularization, but also tissue regeneration and repair. Some agents which we are testing, including a phosphatase inhibitor, orthovanadate, inhibit apoptosis of endothelial cells, promote vascularization in vivo, and may be useful agents to prevent age-associated tissue damage or degeneration.
