Home LiteratureArticle Details
PMID: 8287616 Published · ppublish English Journal Article

The stable prostacyclin analogue Cicaprost inhibits metastasis to lungs and lymph nodes in the 13762NF MTLn3 rat mammary carcinoma.

Clinical & experimental metastasis ·Vol. 12 ·No. 1 ·1994-01-00 ·Pages 24-30

Schirner M, Lichtner RB, Schneider MR

Abstract

Prostacyclin and its stable analogues have been shown to interfere specifically with certain steps of the metastatic cascade. The antimetastatic activity of the stable prostacyclin analogue Cicaprost (Schering AG) on haematogenous metastasis in a series of tumours in rats and mice has been well established. In order to test the effect of Cicaprost on lymphogenous metastasis we chose the metastatic cell clone MTLn3 derived from the 13762NF rat mammary carcinoma. The effect of Cicaprost on prevention of lung metastasis, lymph node metastasis and primary tumour growth was investigated. Cicaprost given in daily doses of 0.01, 0.03 and 0.1 mg/kg orally, reduced the number of lung metastases in a dose-dependent manner. Whereas the median number of lung metastases in the controls was greater than 1000, Cicaprost at a dose of 0.1 mg/kg reduced 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 axillary 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 inhibits lymph node metastasis.

MeSH Terms
Animals Antineoplastic Agents/therapeutic use Dose-Response Relationship, Drug Epoprostenol/analogs & derivatives,therapeutic use Female Lung Neoplasms/prevention & control,secondary Lymphatic Metastasis/prevention & control Mammary Neoplasms, Experimental/drug therapy,pathology Mopidamol/therapeutic use Rats Rats, Inbred F344
Chemicals
Antineoplastic Agents Mopidamol Epoprostenol cicaprost
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Schirner M
Research Laboratories of Schering AG, Berlin, Germany.
Lichtner R B
Schneider M R
References (28)
28 references, click to expand
  1. Cicaprost inhibits metastases of animal tumors.
    Prostaglandins. 1991 Nov;42(5):451-61 PMID: 1763201
  2. Effects of prostacyclin analogues in in vivo tumor models.
    Adv Prostaglandin Thromboxane Leukot Res. 1991;21B:901-8 PMID: 1705084
  3. Pharmacology and endogenous roles of prostaglandin endoperoxides, thromboxane A2, and prostacyclin.
    Pharmacol Rev. 1978 Sep;30(3):293-331 PMID: 116251
  4. Inhibition of tumor cell metastasis by modulation of the vascular prostacyclin/thromboxane A2 system.
    Clin Exp Metastasis. 1983 Apr-Jun;1(2):103-14 PMID: 6242706
  5. Eighth Gaddum Memorial Lecture. University of London Institute of Education, December 1980. Biological importance of prostacyclin.
    Br J Pharmacol. 1982 May;76(1):3-31 PMID: 7044460
  6. Role of plasma, platelets, and endothelial cells in tumor metastasis.
    Cancer Metastasis Rev. 1984;3(2):99-114 PMID: 6386144
  7. Antimetastatic action of the prostacyclin analog iloprost in the mouse.
    Clin Exp Metastasis. 1989 Nov-Dec;7(6):671-8 PMID: 2476273
  8. Warfarin inhibits metastasis of Mtln3 rat mammary carcinoma without affecting primary tumour growth.
    Br J Cancer. 1989 Feb;59(2):179-83 PMID: 2930682
  9. Modulation of human platelet adenylate cyclase by prostacyclin (PGX).
    Prostaglandins. 1977 Mar;13(3):377-88 PMID: 191876
  10. Growth of rat mammary adenocarcinoma cells in semisolid clonogenic medium not correlated with spontaneous metastatic behavior: heterogeneity in the metastatic, antigenic, enzymatic, and drug sensitivity properties of cells from different sized colonies.
    Cancer Res. 1988 Jan 15;48(2):399-404 PMID: 2825974
  11. Functional role of platelets in experimental metastasis studied with cloned murine fibrosarcoma cell variants.
    Cancer Res. 1988 Mar 15;48(6):1460-4 PMID: 3345518
  12. Prostacyclin: a potent antimetastatic agent.
    Science. 1981 Jun 12;212(4500):1270-2 PMID: 7015512
  13. Warfarin inhibition of metastasis: the role of anticoagulation.
    Br J Surg. 1987 Oct;74(10):879-83 PMID: 3664218
  14. Pharmacokinetics and pharmacodynamics of cicaprost in healthy volunteers after oral administration of 5 to 20 micrograms.
    Eur J Clin Pharmacol. 1990;39(2):149-53 PMID: 2253664
  15. Drug treatments for metastasis of the Lewis lung carcinoma: lack of correlation between inhibition of lung metastasis and survival.
    Cancer Res. 1989 Aug 15;49(16):4509-16 PMID: 2743339
  16. Synthesis of a new chemically and metabolically stable prostacyclin analogue with high and long-lasting oral activity.
    J Med Chem. 1986 Mar;29(3):313-5 PMID: 2419560
  17. The eicosanoids and their biochemical mechanisms of action.
    Biochem J. 1989 Apr 15;259(2):315-24 PMID: 2655580
  18. Pharmacological profile of a novel carbacyclin derivative with high metabolic stability and oral activity in the rat.
    Prostaglandins. 1986 Jan;31(1):95-109 PMID: 3513260
  19. Tumor-cell-platelet aggregation does not correlate with metastatic potential of rat 13762NF mammary adenocarcinoma tumor cell clones.
    Int J Cancer. 1984 Jul 15;34(1):101-5 PMID: 6746111
  20. Prostacyclin and thromboxanes. Implications for their role in tumor cell metastasis.
    Biochem Pharmacol. 1983 Jan 1;32(1):1-11 PMID: 6338880
  21. Hormones and breast cancer.
    Recent Prog Horm Res. 1966;22:351-79 PMID: 5334629
  22. Adherence of leucocytes to electrically damaged venules in vivo. Effects of iloprost, PGE1, indomethacin, forskolin, BW 755 C, sulotroban, hirudin, and thrombocytopenia.
    Eicosanoids. 1988;1(1):13-7 PMID: 2483344
  23. Differential organ tissue adhesion, invasion, and growth properties of metastatic rat mammary adenocarcinoma cells.
    Breast Cancer Res Treat. 1988 Oct;12(2):167-76 PMID: 3242647
  24. The prostacyclin analogue cicaprost inhibits metastasis of tumours of R 3327 MAT Lu prostate carcinoma and SMT 2A mammary carcinoma.
    J Cancer Res Clin Oncol. 1992;118(7):497-501 PMID: 1624541
  25. Platelet-tumor cell interaction: effect of prostacyclin and a synthetic analog on metastasis formation.
    Cancer Chemother Pharmacol. 1988;22(4):289-93 PMID: 2458854
  26. Antiplatelet pyrimido-pyrimidines and metastasis.
    Cancer Treat Rev. 1985 Dec;12(4):221-34 PMID: 3009013
  27. Development and biologic properties of malignant cell sublines and clones of a spontaneously metastasizing rat mammary adenocarcinoma.
    J Natl Cancer Inst. 1982 Mar;68(3):507-17 PMID: 6950180
  28. Effects of RA 233 treatment on the adhesive, invasive and metastatic properties of 13762NF rat mammary tumor cells.
    Clin Exp Metastasis. 1989 Mar-Apr;7(2):175-86 PMID: 2920474
Article Info
Journal
Clinical & experimental metastasis
Abbr.
Clin Exp Metastasis
ISSN
0262-0898
Published
1994-01-00
Pages
24-30
Language
English
Region
Netherlands
NLM ID
8409970
Subset
IM
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]