ANTIMETASTATIC ACTION OF THE PROSTACYCLIN ANALOG CICAPROST IN EXPERIMENTAL MAMMARY-TUMORS

In breast cancer, the survival rate strongly depends on the number of lymph nodes involved. A drug with a specific inhibitory activity on ly mph node and organ metastases would therefore be a candidate for adjuv ant therapy after surgery. Prostacyclin and its stable analogues have been shown to interfere with certain steps of the metastatic cascade a nd to inhibit the number of lung colonies after i.v.-inoculation of va rious tumor cell lines. Our data reveal that cicaprost, a metabolicall y stable and orally active analogue of prostacyclin, has pronounced an timetastatic effects in a series of spontaneously metastasizing rodent tumors. In the SMT 2a and 13762 MTLn3 mammary carcinomas of the rat, cicaprost given daily from the day of tumor implantation strongly inhi bits the number of lung metastases as well as lymph node weights witho ut exerting an effect on the primary tumor. Even starting treatment wh en palpable primary tumors are present gives a pronounced antimetastat ic activity. To demonstrate that cicaprost has an effect on metastases already settled in the respective organ, treatment was started after surgical removal of the primary tumor. In the SMT 2a tumor, a strong i nhibition of the number of metastases was shown. Interestingly, a peri operative treatment schedule was also effective in both models used. A s primary tumor growth in vivo or proliferation in vitro remained unch anged by cicaprost, its mode of action seems to be related to one or m ore mechanisms of the metastatic process. In tumor cell lines expressi ng a functional prostacyclin receptor, stimulated tumor cell migration is inhibited and changes of differentiation status are obvious. In co nclusion, cicaprost strongly inhibits lymph node and organ metastases of spontaneously metastasizing rodent mammary tumors with a mode of ac tion different from cytostatic or antihormonal drugs.