Influence of pertussis toxine on local progression and metastasis after orthotopic implantation of the human prostate cancer cell line PC3 in nude mice

Tumor cell migration is a fundamental process of metastasis. Pertussis toxi ne inhibits lysophosphatidic acid related cell migration by ADP-ribosylatio n of G proteins. We examined the influence of pertussis toxine (PTX) on pro gression and metastasis of the human hormone-insensitive prostate cancer ce ll line PC-3 after orthotopic implantation in nude mice. In 30 athymic male nude mice (NMRI) 5 x 10(5) PC-3 cells were injected into the dorsal prostate. After 7d 15 mice received a total of six intraperiton eal injections of 5 mu g PTX/100 g body weight at an interval of 4 d. The o ther 15 mice received phosphate buffered saline and served as control. All mice were killed at 37 d followed by macroscopical and histological evaluat ion of local tumor growth and metastasis. In the control group tumorigenicity was 100%; (15 out of 15). Mean weight o f the tumor bearing unit of prostate and seminal vesicles was 541mg (243-76 3 mg). The rate of positive lymphnodes was 100% with a mean transversal dia meter of 3.9 mm (1.2-5.4 mm). In the PTX group local take rate was 100% wit h a mean weight of 251mg (88-478 mg) (P two sided <0.0001). The rate of pos itive lymphnodes was 60% (9 out of 15) (P = 0.017) with a mean transversal diameter of 2.3 mm (1.0-4.5 mm). PTX following orthotopic implantation of the human hormone-insensitive PC-3 cell line significantly reduces local tumor growth as well as metastasis t o locoregional lymphnodes.