A program to study the relationship between aging and cancer was initiated in the laboratory. Three human prostatic carcinoma cell lines did not grow when injected in nude mice at levels of 500,000 cells/mouse. However, we obtained very rapid growth of the cells when injected as a suspension with basement membrane. Attempts to address the mechanisms(s) of growth stimulation are on-going and include the effect of laminin peptides and antimacrophage serum on growth. We are also using isolated primary prostate biopsy tissue to determine if cells from this source will also be stimulated to grow in the presence of extracellular matrix. The growth of tumors in aged mice was studied using C57BL/6 mice and melanoma cells. These cells were grown subcutaneously and growth was enhanced when cells were injected with extracellularmatrix molecules, but enhancement was 3.5-fold more pronounced in 6 month old animals compared to 12, 18, and 24 month old animals. Further experiments will examine the dose dependence of growth in the aged animals in order to understand the basis for these age-related effects. To examine the initial steps in the metastatic process, microvasculature endothelial cells were isolated from bovine retina and cultured with growth supplements. Activated endothelia was then used to examine tumor cell binding in an in vitro assay. These studies will be extended to test inhibitors of glycosylation for their effect on tumor cell adhesion.
