ANDROGEN-INDEPENDENT CANCER PROGRESSION AND BONE METASTASIS IN THE LNCAP MODEL OF HUMAN PROSTATE-CANCER

Our laboratory has previously reported on the derivation of LNCaP cell sublines from LNCaP tumors maintained in castrated and intact athymic male mice. These LNCaP sublines differ from the parental line in tumo rigenicity and androgen dependence. This paper demonstrates that one o f these sublines acquired metastatic potential. When inoculated either s.c. or orthotopically, the C4-2 subline metastasized to the lymph no de and bone with an incidence of 11-50%. Interestingly, the incidence of osseous metastasis was higher in castrated than in intact male host s. We evaluated the chromosomal, immunohistochemical, and biochemical characteristics of the LNCaP sublines derived from C4-2 tumors that me tastasized to the lymph node and bone. Cytogenetic analysis showed tha t all sublines were human and shared common marker chromosomes with th e parental LNCaP cells. This experimental human prostate cancer model may permit, for the first time, the study of the molecular mechanisms underlying human prostate cancer metastasis.