Murine mammary carcinoma 4T1 induces a leukemoid reaction with splenomegaly: Association with tumor-derived growth factors
Murine mammary carcinoma 4T1 induces a leukemoid reaction with splenomegaly: Association with tumor-derived growth factors
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DOI：
10.1016/j.yexmp.2006.06.007
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发表时间：
2007-02-01
影响因子：
3.6
通讯作者：
Hunter, Kenneth W., Jr.
中科院分区：
文献类型：
--
作者：
duPre', Sally A.;Hunter, Kenneth W., Jr.
在动物和患有多种肿瘤的人身上观察到粒细胞减少和脾肿大的类白血病反应。我们采用四色流式细胞术对BALB/c雌性小鼠可移植小鼠乳腺癌4T1诱导的类白血病反应进行了表征。外周血中具有粒细胞形态的Gr-1（+）髓样细胞从移植前的< 15%增加到移植后四周CD45（+）白细胞总数的近80%。外周血中CD19(+) B淋巴细胞、CD4（+）和CD8(+) T淋巴细胞的绝对数量及CD4/CD8比值均无明显变化，但粒细胞与淋巴细胞比值明显升高。荷瘤小鼠股骨脂肪性骨髓呈髓样增生。具有Gr-1（暗）/CD11b（亮）未成熟粒细胞表型的细胞显著增加，这些细胞也见于外周血和脾脏。肿瘤移植后4周脾脏重量增加8.5倍，主要原因是粒细胞增生。培养的4T1肿瘤细胞组成性地表达髓系集落刺激因子G-CSF和GM-CSF的mRNA，并检测到ifn - γ诱导的M-CSF转录物。小鼠切除的肿瘤有G-CSF和GM-CSF的转录本，但在荷瘤小鼠的血清中只发现高水平的G-CSF蛋白。这些数据表明，4T1荷瘤小鼠表现出白血病样反应，这显然是由肿瘤产生的集落刺激因子引起的。4T1肿瘤可能是研究该反应的一个很好的模型。(c) 2006爱思唯尔公司版权所有。
A leukemoid reaction with granulocytosis and splenomegaly has been observed in animals and humans with a variety of tumors. We have employed four color flow cytometry to characterize the leukemoid reaction induced by the transplantable mouse mammary carcinoma 4T1 in female BALB/c mice. Gr-1(+) myeloid cells with the morphology of granulocytes increased in peripheral blood from < 15% pre-transplant to nearly 80% of total CD45(+) leukocytes at four weeks post-transplant. Though the granulocyte: lymphocyte ratio increased markedly, the absolute numbers of CD19(+) B lymphocytes, CD4(+) and CD8(+) T lymphocytes, and the CD4/CD8 ratio in peripheral blood did not change significantly. Femurs from tumor-bearing mice showed myeloid hyperplasia of the fatty marrow. There was a notable increase in cells with a Gr-1(dim)/CD11b(bright) immature granulocyte phenotype, and these cells were also found in peripheral blood and spleen. Spleen weights had increased 8.5-fold by four weeks post-tumor transplant, mainly due to granulocytic hyperplasia. Cultured 4T1 tumor cells constitutively expressed mRNA for the myeloid colony-stimulating factors G-CSF and GM-CSF, and IFN-gamma-inducible M-CSF transcripts were also detected. Tumors excised from mice had transcripts for G-CSF and GM-CSF, but only G-CSF protein was found in high levels in serum of tumor-bearing mice. These data demonstrate that 4T1 tumor-bearing mice exhibit a leukemoid reaction that apparently is caused by the production of colony-stimulating factors produced by the tumor. The 4T1 tumor may serve as an excellent model for the study of this reaction. (c) 2006 Elsevier Inc. All rights reserved.