Early events of hepatic metastasis formation in mice:: Role of Kupffer and NK-cells in natural and interferon-γ-stimulated defense
Early events of hepatic metastasis formation in mice:: Role of Kupffer and NK-cells in natural and interferon-γ-stimulated defense
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DOI：
10.1006/jsre.1998.5532
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发表时间：
1999-04-01
影响因子：
2.2
通讯作者：
Smedsrod，B
中科院分区：
文献类型：
--
作者：
Rushfeldt，C;Sveinbjornsson，B;Smedsrod，B
肿瘤的手术操作可能导致肿瘤细胞流入全身和门静脉循环的增加，并引起转移瘤的形成。此外，据报道，大手术会引起严重的免疫抑制。为了增强术后宿主抗肿瘤免疫机制，我们研究了术前给予干扰素-γ的效果，其与枯否细胞（KC）和自然杀伤细胞（NK-细胞）在肝转移形成早期的抗转移作用有关。将结肠癌细胞注射到同系小鼠的上级肠系膜静脉中，17天后通过重量、数量和[125 I]碘脱氧尿苷的摄取来定量转移。将结肠癌细胞注射到同系小鼠的上级肠系膜静脉中后17天，未受刺激的对照小鼠每个肝脏产生10.5个表面结节。在接种肿瘤细胞前4 h用1000 IU IFN-γ单次剂量刺激的小鼠中，该数字仅为2.6。在肿瘤细胞接种前24小时给予GdCl 3（据报道可消耗和阻断枯否细胞的功能）导致肿瘤质量相对于对照增加5倍。注射抗-asiolo-GM 1抗血清，消除肝脏NK细胞，诱导肿瘤质量增加10倍。这些结果表明肝脏NK细胞和KC具有重要的早期抗转移功能，并且手术前给予IFN-γ对于消除循环肿瘤细胞和抑制残留肿瘤的发展可能很重要。
Surgical manipulation of a tumor may result in increased influx of tumor cells into the systemic and portal circulation and give rise to formation of metastases. In addition, major surgery has been reported to cause profound immunosuppression. In an attempt to increase the host–antitumor immune mechanisms following surgery we have studied the effect of preoperative administration of interferon-γ, related to the antimetastatic effects of Kupffer cells (KC) and natural killer cells (NK-cells) in the early phase of liver metastasis formation. Colon carcinoma cells were injected into the superior mesenteric vein of syngeneic mice and after 17 days metastases were quantified by weight, number, and uptake of [125I]iododeoxyuridine. Unstimulated control mice developed 10.5 surface nodules per liver 17 days following injection of colon carcinoma cells into the superior mesenteric vein of syngeneic mice. This figure was only 2.6 in mice stimulated with a single dose of 1000 IU IFN-γ 4 h prior to inoculation of tumor cells. Administration of GdCl3, which is reported to deplete and block the function of Kupffer cells, 24 h prior to tumor cell inoculation resulted in a 5-fold tumor mass increase relative to control. Injection of anti-asiolo-GM1antiserum, which eliminates the hepatic NK-cells, induced a 10-fold increase in tumor mass. These results indicate an important early antimetastatic function of hepatic NK-cells and KC and that presurgical administration of IFN-γ may be important for eliminating circulating tumor cells and inhibiting development of residual tumors.