THE STABLE PROSTACYCLIN ANALOG CICAPROST INHIBITS METASTASIS TO LUNGSAND LYMPH-NODES IN THE 13762NF MTLN3 RAT MAMMARY-CARCINOMA

Prostacyclin and its stable analogues have been shown to interfere spe cifically with certain steps of the metastatic cascade. The antimetast atic activity of the stable prostacyclin analogue Cicaprost (Schering AG) on haematogenous metastasis in a series of tumours in rats and mic e has been well established. In order to test the effect of Cicaprost on lymphogenous metastasis we chose the metastatic cell clone MTLn3 de rived from the 13762NF rat mammary carcinoma. The effect of Cicaprost on prevention of lung metastasis, lymph node metastasis and primary tu mour growth was investigated. Cicaprost given in daily doses of 0.01, 0.03 and 0.1mg/kg orally, reduced the number of lung metastases in a d ose-dependent manner. Whereas the median number of lung metastases in the controls was greater than 1000, Cicaprost at a dose of 0.1mg/kg re duced the number of lung metastases to between 11 and 100. The weight of the ipsilateral axillary lymph nodes was diminished by Cicaprost to 30-50% of controls. Moreover, metastasis to the contralateral axillar y lymph node was completely inhibited by Cicaprost at all three doses tested. Cicaprost did not influence the growth rate of the MTLn3 cell clone implanted into the mammary fat pad or the weight of the primary tumour at the end of treatment, In conclusion, in addition to its dose -dependent effect on haematogenous metastasis, Cicaprost strongly inhi bits lymph node metastasis.