ABSTRACT
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 tumorigenicity and androgen dependence. This paper demonstrates that one of these sublines acquired metastatic potential. When inoculated either s.c. or orthotopically, the C4-2 subline metastasized to the lymph node and bone with an incidence of 11-50%. Interestingly, the incidence of osseous metastasis was higher in castrated than in intact male hosts. We evaluated the chromosomal, immunohistochemical, and biochemical characteristics of the LNCaP sublines derived from C4-2 tumors that metastasized to the lymph node and bone. Cytogenetic analysis showed that all sublines were human and shared common marker chromosomes with the 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.
Subject(s)
Bone Neoplasms/secondary , Osteosarcoma/secondary , Prostatic Neoplasms , Animals , Bone Neoplasms/genetics , Humans , Karyotyping , Lymphatic Metastasis , Male , Mice , Mice, Inbred BALB C , Mice, Nude , Neoplasm Transplantation , Orchiectomy , Osteosarcoma/genetics , Paraplegia/etiology , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathology , Tumor Cells, CulturedABSTRACT
Neuroendocrine (NE) differentiation within the primary prostate tumor has been correlated with tumor progression and shortened patient survival. Serotonin (5-hydroxytryptamine, 5-HT), a known mitogen, is found in most neuroendocrine cells of the human prostate. We have previously found that human prostatic carcinoma cell lines, PC-3, DU-145 and LNCaP, display certain NE characteristics. In this study, we have examined the effects of several subtype-selective 5-HT receptor antagonists on the growth of the three lines. Of these, the 5-HT1A antagonist pindobind had the most marked antiproliferative effect in vitro. Pindobind also had marked growth-inhibitory effects on the aggressive PC-3 cell line in vivo, in athymic nude mice. Radioligand binding studies indicated the presence of 5-HT binding sites on all three cell lines. Our results suggest that 5-HT is involved in the growth of prostate tumor cells and may serve as a target for treatment.
Subject(s)
Prostatic Neoplasms/pathology , Serotonin Antagonists/pharmacology , Cell Division/drug effects , Cyclohexane Monoterpenes , Humans , Male , Pindolol/analogs & derivatives , Pindolol/pharmacology , Prostatic Neoplasms/chemistry , Radioligand Assay , Receptors, Serotonin/analysis , Tumor Cells, CulturedABSTRACT
Cystinuria is a rare cause of renal calculi, whose management presents a complex problem mainly due to the hardness and high recurrence rate of cystine stones. During the period 1987-1991, 28 established cases of cystine calculi were treated by extracorporeal shock wave lithotripsy (ESWL) and percutaneous nephrolithotripsy (PCNL). These cases were divided into 5 groups, according to the position and size of the stones, and each group then followed a specific regimen, either ESWL monotherapy or a combined treatment comprising an initial ESWL treatment followed by PCNL or vice versa. ESWL monotherapy provided satisfactory results only in the group with pelvic stones (54.5% success rate), with 2.16 stone treatments/renal unit, and only with calculi smaller than 2.5 cm. The groups with multiple stones or staghorn calculi were treated with a combined treatment of ESWL and PCNL and had success rates of 50 and 67%, respectively. However, the group in which PCNL was followed by ESWL showed a clear advantage over the group in which ESWL was administered before PCNL, since it required a smaller number of ESWL treatments (1,5 stone treatments/renal unit as compared to 4.3 stone treatments/renal unit). Finally, attempts for ESWL in situ in the few cases of ureteral stones proved unsuccessful.