Tumor growth, angiogenesis and inflammation in mice lacking receptors for platelet activating factor (PAF)
Tumor growth, angiogenesis and inflammation in mice lacking receptors for platelet activating factor (PAF)
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DOI：
10.1016/j.lfs.2007.05.003
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发表时间：
2007-06-27
期刊：
影响因子：
6.1
通讯作者：
Andrade, S. P.
中科院分区：
文献类型：
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作者：
Ferreira, M. A. N. D.;Barcelos, L. S.;Andrade, S. P.
肿瘤生长与血管生成和炎症有关，内源性脂质血小板活化因子（PAF）是促炎症和促血管生成的介质。因此，我们测量了正常（WT）小鼠和通过基因缺失（PAFR-KO）缺乏PAF受体的小鼠的肿瘤生长，血管生成和炎症。相对于WT品系，PAFR-KO小鼠中源自结肠26细胞的实体瘤生长未改变，但源自埃利希细胞的实体瘤生长显著增加（5倍）。血管生成，作为VEGF或血红蛋白的肿瘤含量，在来自突变株的两个肿瘤中增加。肿瘤中的炎症（如中性粒细胞和巨噬细胞积聚以及肿瘤的趋化因子（CXCL 2和CCL 2）含量）减少或不变，这意味着PAFR-KO菌株中的炎症反应总体减少。我们还评估了腹腔注射后埃利希肿瘤在腹水中的生长情况。在此，生长（腹水体积）被抑制约30%，但PAFR-KO小鼠腹水中的中性粒细胞和巨噬细胞数量增加。在突变株中，未被肿瘤细胞侵袭的腹膜壁中的血管生成增加，但白细胞浸润减少。我们的研究结果出乎意料地显示，在对PAF缺乏反应的小鼠中，肿瘤诱导的血管生成增加，由此我们推断，在正常（WT）小鼠中，PAF是抗血管生成的。此外，尽管PAFR-KO小鼠的生长仍与血管生成相关，但生长与炎症（白细胞蓄积）无关。(C)2007年爱思唯尔公司All rights reserved.
Tumor growth is associated with angiogenesis and inflammation and the endogenous lipid, platelet activating factor (PAF), is a proinflammatory and pro-angiogenic mediator. We therefore measured tumor growth, angiogenesis and inflammation in normal (WT) mice and those lacking the receptor for PAF, through gene deletion (PAFR-KO). Growth of solid tumors derived from colon 26 cells was not altered but that from Ehrlich cells was markedly (5-fold) increased in the PAFR-KO mice, relative to the WT strain. Angiogenesis, as tumor content of VEGF or hemoglobin, was increased in both tumors from the mutant strain. Inflammation, as neutrophil and macrophage accumulation and chemokine (CXCL2 and CCL2) content of tumors, was decreased or unchanged in the tumors implying an overall decrease in the inflammatory response in the PAFR-KO strain. We also assessed growth of the Ehrlich tumor in its ascites form, after i.p. injection. Here growth (ascites volume) was inhibited by about 30%, but neutrophil and macrophage numbers were increased in the ascites fluid from the PAFR-KO mice. Angiogenesis in the peritoneal wall, which is not invaded by the tumor cells, was increased but leukocyte infiltration decreased in the mutant strain. Our results show, unexpectedly, that tumor-induced angiogenesis was increased in mice lacking response to PAF, from which we infer that in normal (WT) mice, PAF is anti-angiogenic. Further, although growth was still associated with angiogenesis in PAFR-KO mice, growth was not correlated with inflammation (leukocyte accumulation). (C) 2007 Elsevier Inc. All rights reserved.