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

Schirner, Michael; Lichtner, Rosemarie B.; Schneider, Martin

doi:10.1007/bf01784330

Cited by 9 publications

(4 citation statements)

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“…48 Additional studies revealed that cicaprost, a metabolically stable and orally active analogue of prostacyclin, has prominent antimetastatic effects in a series of spontaneously metastasising mammary carcinomas of experimental animals (rat, mouse) and it reduce the median number of metastases from other tumor types. 93,95,96 The mechanism of action of cicaprost is different from cytostatic drugs, because primary tumor growth in vivo or proliferation in vitro remained unchanged. Finally, cicaprost can be used in combination with cytostatic drugs (cyclophosphamide, doxorubicin or 5-FU), without interfering with inhibition of tumor growth.…”

Section: Role Of a Nticoagulants And I Nhibitors Of P Latelet A Ggregmentioning

confidence: 99%

“…Finally, cicaprost can be used in combination with cytostatic drugs (cyclophosphamide, doxorubicin or 5-FU), without interfering with inhibition of tumor growth. 94,96 Experimental and clinical studies suggest that heparin and vitamin K antagonists are effective compounds for the prevention of metastases. 33,107 Data from randomised trials suggest that small-cell lung cancer (SCLC) consistently responds to heparin and vitamin K antagonist, but several other tumors, including non small-cell cancer (NSCLC), colon and prostate cancer, do not respond to warfarin 13,11,55,111,117 and do not produce thrombin.…”

Section: Role Of a Nticoagulants And I Nhibitors Of P Latelet A Ggregmentioning

confidence: 99%

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Coagulation and cancer: Implications for diagnosis and management

Loreto

Martinis

Corsi

et al. 2000

Pathol. Oncol. Res.

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Section: Role Of a Nticoagulants And I Nhibitors Of P Latelet A Ggregmentioning

confidence: 99%

Section: Role Of a Nticoagulants And I Nhibitors Of P Latelet A Ggregmentioning

confidence: 99%

Coagulation and cancer: Implications for diagnosis and management

Loreto

Martinis

Corsi

et al. 2000

Pathol. Oncol. Res.

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“…The lung weight was decreased significantly by the two higher doses used (Figure 3). Concerning lymph node metastasis, cicaprost reduced the weight of the ipsilateral axillary lymph nodes to about 50% at all three doses used and the weight of the contralateral lymph nodes to the level of a nontumor bearing animal ( Figure 3) [15].…”

Section: Effect On Experimental Mammary Carcinomasmentioning

confidence: 99%

“…We have shown a correlation of the presence of functional prostacyclin receptors and antimetastatic effects in vivo and in vitro. In vivo, cicaprost exerts a prominent antimetastatic action on MTLn3 mammary carcinomas [15], which have functional prostacyclin receptors, but has no effect on RUCA endometrial carcinomas, which lack functional receptors. In vitro, transendothelial migration of MTLn3 cells is inhibited by cicaprost [19].…”

Section: Mechanism Of Actionmentioning

confidence: 99%

Antimetastatic action of the prostacyclin analogue cicaprost in experimental mammary tumors

Schneider¹,

Schirner²,

Lichtner³

et al. 1996

Breast Cancer Res Tr

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In breast cancer, the survival rate strongly depends on the number of lymph nodes involved. A drug with a specific inhibitory activity on lymph node and organ metastases would therefore be a candidate for adjuvant therapy after surgery. Prostacyclin and its stable analogues have been shown to interfere with certain steps of the metastatic cascade and to inhibit the number of lung colonies after i.v.-inoculation of various tumor cell lines. Our data reveal that cicaprost, a metabolically stable and orally active analogue of prostacyclin, has pronounced antimetastatic 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 inhibits the number of lung metastases as well as lymph node weights without exerting an effect on the primary tumor. Even starting treatment when palpable primary tumors are present gives a pronounced antimetastatic 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 inhibition of the number of metastases was shown. Interestingly, a perioperative treatment schedule was also effective in both models used. As primary tumor growth in vivo or proliferation in vitro remained unchanged by cicaprost, its mode of action seems to be related to one or more mechanisms of the metastatic process. In tumor cell lines expressing a functional prostacyclin receptor, stimulated tumor cell migration is inhibited and changes of differentiation status are obvious. In conclusion, cicaprost strongly inhibits lymph node and organ metastases of spontaneously metastasizing rodent mammary tumors with a mode of action different from cytostatic or antihormonal drugs.

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Inhibition of TPA and 12(S)‐HETE‐stimulated tumor cell adhesion by prostacyclin and its stable analogs: Rationale for their antimetastatic effects

Tang

Grossi

Tang

et al. 1995

Intl Journal of Cancer

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The ability of malignant neoplasms to metastasize is probably the most important obstacle to the survival of the cancer patient. A rate-limiting step in the metastatic cascade is the arrest and adhesion of tumor cells to the endothelium or subendothelial matrix comprising the vessel wall. This process of tumor cell interaction with the vessel wall has been previously analyzed at the molecular level with the "docking and locking" hypothesis . The hypothesis divides tumor cell interaction with target organ endothelium into 2 interdependent yet distinct steps. Initial interaction between rolling tumor cells and the underlying endothelium is mediated by relatively weak and transient adhesions. The second-phase, tighter adhesion, i.e., "locking", relies on adhesion receptors present on both tumor cells and the endothelium and is regulated by various bioactive mediators elaborated by tumor cells, endothelial cells and possibly other host cells such as platelets . Experiments indicate that this second phase is primarily mediated by integrin receptors present on the tumor cells (e.g., aIIbp3; Grossi et a/., 1989) as well as endothelium (e.g., 0593; Tang et a/., 1993a, 1994). Among the many modulators which can influence tumor cell interaction with endothelium are bioactive lipids such as the eicosanoids .Metabolites of arachidonic and linoleic acid have been demonstrated to bidirectionally modulate tumor cell interaction with the endothelium and SEM (Grossi et a!., Liu et al., 1991). Honn et al. (1989) have demonstrated that a lipoxygenase metabolite of arachidonic acid, i.e., 12(S)-HETE, increases tumor cell adhesion to SEM and components of subendothelial matrix. This effect is antagonized by a 15-lipoxygenase metabolite of linoleic acid, i.e., 13(S)-HODE (Grossi et al., 1989; Liu et al., 1991). In fact, bidirectional modulation of integrin receptor expression and tumor cell adhesion by 12(S)-HETE and 13(S)-HODE has been observed at the level of PKC (Liu et al., 1994). In addition to these lipoxygenase metabolites, cyclooxygenase metabolites of arachidonic acid, i.e., PGIz and TXA2, have been shown to modulate tumor cell-vessel interactions as well as metastasis . PG12 is a potent inhibitor of platelet activation and aggregation and is the predominant cyclooxygenase metabolite produced by endothelium. have shown that exogenous PGIl inhibits lung colony formation by murine B16a cells injected i.v. into syngeneic animals. This experimental finding established that PG12 possesses antimetastatic activity and that it may have clinical significance in oncology. In addition, Honn et a/. (1983) proposed that endogenous production of PGIz by endothelium may constitute a natural deterrent to hematogenous metastasis. Since those initial studies the anti-metastatic effects of PGI2 and PG12 analogs have been observed in a wide spectrum of tumor cells from different species and of different histopathological types (reviewed in Honn et al., 1992). It has been previously shown by our laboratory that 12(S)-HETE and TPA increase surfa...

show abstract

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

Cited by 9 publications

References 26 publications

Coagulation and cancer: Implications for diagnosis and management

Coagulation and cancer: Implications for diagnosis and management

Antimetastatic action of the prostacyclin analogue cicaprost in experimental mammary tumors

Inhibition of TPA and 12(S)‐HETE‐stimulated tumor cell adhesion by prostacyclin and its stable analogs: Rationale for their antimetastatic effects

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