SPONTANEOUS METASTASIS OF PC-3 CELLS IN ATHYMIC MICE AFTER IMPLANTATION IN ORTHOTOPIC OR ECTOPIC MICROENVIRONMENTS

The ability of subcutaneous, prostatic, and nonprostatic intraabdomina l organ microenvironments to influence local tumor growth and metastas is of PC-3 human prostate carcinoma cells in athymic mice was determin ed. Tumorigenesis and metastasis of PC-3 were evaluated 60 days after subcutaneous and intraprostatic (orthotopic) implantation of 5 x 10(5) PC-3 cells in 6-week-old, male athymic mice. Intraprostatic implantat ion of PC-3 cells resulted in paraaortic lymph node metastases in 10 o f 10 (100%) mice with prostatic tumors, whereas metastases were presen t in only 2 of 9 (22%) mice after subcutaneous implantation. Next, we determined whether the urinary bladder (nonprostatic, urogenital micro environment) or stomach (nonurogenital, intraabdominal microenvironmen t) would facilitate the metastasis of PC-3 cells in athymic mice. Tumo rigenesis and metastasis were 100% after subserosal implantation of PC -3 cells within the wall of the urinary bladder (n = 6 mice). Subseros al implantation of PC-3 cells into the stomach wall (n = 7 mice) also resulted in tumor formation and metastasis to regional lymph nodes in 100% of mice. In all experiments, regional lymph nodes were the most f requent site of metastasis, regardless of implantation site. We conclu de that tumor microenvironment factors responsible for the metastasis of PC-3 cells in athymic mice may not be organ-specific, since nonpros tatic visceral microenvironments are sufficient for predictable metast asis. Use of these models may further our understanding of how tumor m icroenvironment modulates expression of the metastatic phenotype by hu man prostate carcinoma cells. (C) 1995 Wiley-Liss, Inc.