Effect of defibrinogenation on tumor growth and metastasis in mice
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Blood coagulation-fibrinolysis system is of great importance on tumor growth and metastasis. Our previous studies on the inhibition of metastases by sulfated polysaccharides have shown that intravascular coagulation was a very important mechanism at an early stage of hematogenous metastasis.For the purpose of investigating the significance of fibrinogen on tumor growth and metastasis, we studied effect of defibrinogenation with ancrod in mice. Lewis lung tumor (3LL) is a favorable model of pulmonary metastases in syngeneic C57BL/6 mice. Therefore, 3LL cells were inoculated via tail vein for intravenously induced pulmonary metastases or subcutaneously implanted into foot pad for those of spontaneity.Primary tumor was amputated 9 or 12 days after tumor implantation. Mice were autopsied on day 14 after intravenous tumor inoculation or day 23 after tumor implantation into foot pad. Pulmonary metastases were assayed grossly by counting the number of pulmonary surface nodules and measuring dry weight of metastatic lungs.Our experimental results for ancrod on tumor growth and metastases are as follows. Significant reduction of intravenously induced pulmonary metastases in mice treated with 200units/kg of ancrod once intraperitoneally, one hour before tumor inoculation (P<0.001). Plasma fibrinogen levels decreased to the extent of trace in the first 4 hours and was 55mg/dl in 12 hours after administration in mice treated with same dose of ancrod. Furthermore, significant reduction of spontaneous pulmonary metastases was obtained in mice treated with 200units/kg of ancrod twice daily for post-amputation period starting from day 15 to 22 after tumor implantation (P<0.01). However, no inhibition of spontaneous metastases was observed in mice treated for only pre-amputation, and pre-and post-amputation period. Plasma fibrinogen levels increased prominently after tumor amputation in mice. On the contrary, those were less than 71mg/dl in all mice bearing 3LL treated with ancrod. No inhibition of primary tumor was observed at the time of amputation. The significance of fibrinogen on tumor growth and metastasis was discussed.
- 一般社団法人 日本血栓止血学会の論文
一般社団法人 日本血栓止血学会 | 論文
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