Effects of vitamin D and retinoids on the differentiation and growth in vitro of canine osteosarcoma and its clonal cell lines

Although canine osteosarcoma is one of the most malignant, aggresive and le thal neoplasms originating from undifferentiated bone cells, it may retain some capacity for normal differentiation. The purpose of this study was to ascertain if the residual capacity for differentiation could be used to sup press its malignant properties. We tested the efficacy of vitamin D and ret inoids in inducing differentiation and inhibiting growth of the POS canine osteosarcoma and four of its clonal cell lines, POS 14A (fibroblast type), POS 53B (chondroblast type), POS 53C (undifferentiated type) and POS 53D (o steoblastic type). Treatment with 10(-10) to 10(-8)M concentrations of calc itriol, OCT, cholecalciferol, all-trans retinoic acid (ATRA) and 9-cis reti noic acid for 48-120 hours changed the morphology of POS, POS 53B, POS 53C and POS 53D cells to cells that were elongated and spindle-shaped. Increase d number of cytoplasmic organelles and pronounced nuclear activities were i nduced by concentrations of 10(-8)M and 10(-7)M for 120 hours. All drugs at concentrations of 10(-10) to 10(-8)M for 72 hours inhibited POS growth dos e-dependently. OCT significantly reduced the cell number in all cell lines when used at concentrations between 10(-9) and 10(-8)M for 72 hours and exe rted significant anti-proliferative effects for eight days culture. This st udy demonstrated that changed morphology and inhibition of growth was induc ed by treatment of the cells with these vitamins, that the loss of control of differentiation in the neoplasia was not irreversible and that these dru gs may be useful in the clinic.