ANTIMETASTATIC AND ANTITUMOR ACTIVITIES OF INTERLEUKIN-10 IN TRANSFECTED HUMAN PROSTATE PC-3 ML CLONES - ORTHOTOPIC GROWTH IN SEVERE COMBINED IMMUNODEFICIENT MICE

We have permanently transfected human prostate PC-3 hit tumor cells an d examined the influence of interleukin 10 (IL-10) production on tumor growth and metastasis following orthotopic implantation in the prosta te gland of severe combined immunodeficient mice. Measurements of tumo r volume after 5, 8, and 12 weeks indicated that tumor volume was nega tively correlated with the amount of IL-10 production. Likewise, the e xtent of metastasis was inversely related to the amount of IL-10 produ ced. Following i.v. injection, the IL-10-expressing clones also failed to metastasize to the bone marrow. Controls showed that PC-3 ML and P C-3 ML mock clones grew rapidly and metastasized when implanted orthot opically or injected i.v, via the tail vein. Mouse survival curves sho wed that all of the mice injected orthotopically with the PC-3 hit clo nes died by about 14-16 weeks, whereas the PC-3 ML-IL10a or PC-3 ML-IL 10b clones induced only 10-20% death after 23-24 weeks, Likewise, surv ival studies showed a high death rate by similar to 30 days with PC-3 ML mock cells but <10% death by 12 weeks with the IL-TO-transfected cl ones injected i.v, via the tail vein. The data strongly suggest that I L-10 production blocks tumor growth and metastasis in severe combined immunodeficient mice.