Zoledronic acid repolarizes tumour-associated macrophages and inhibits mammary carcinogenesis by targeting the mevalonate pathway.
Zoledronic acid repolarizes tumour-associated macrophages and inhibits mammary carcinogenesis by targeting the mevalonate pathway.
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DOI：
10.1111/j.1582-4934.2009.00926.x
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发表时间：
2010-12
影响因子：
5.3
通讯作者：
Massaia M
中科院分区：
文献类型：
--
作者：
Coscia M;Quaglino E;Iezzi M;Curcio C;Pantaleoni F;Riganti C;Holen I;Mönkkönen H;Boccadoro M;Forni G;Musiani P;Bosia A;Cavallo F;Massaia M
目前尚不清楚临床相关剂量的唑来膦酸（ZA）是否对骨外肿瘤有活性。用相当于人类推荐剂量的累积剂量对活化ErbB-2癌基因转基因小鼠进行治疗。在用ZA处理的小鼠中观察到无肿瘤存活和总体存活的显著增加。在临床相容浓度下，ZA调节甲羟戊酸途径并影响肿瘤细胞和巨噬细胞中的蛋白质异戊二烯化。肿瘤相关巨噬细胞数量的显著减少被肿瘤血管形成的显著减少所掩盖。局部血管内皮生长因子和白细胞介素-10的产生急剧下调，有利于干扰素-γ的产生。腹膜巨噬细胞和肿瘤相关的巨噬细胞ZA治疗的小鼠恢复了完整的M1抗肿瘤表型，如核转位的核因子kB，诱导型一氧化氮合酶的表达和一氧化氮的生产。这些数据表明，临床上可达到的ZA剂量通过靶向局部微环境抑制自发性乳腺癌发生，如肿瘤血管形成减少、肿瘤相关巨噬细胞数量减少及其从M2表型到M1表型的逆转极化所示。
It is unknown whether zoledronic acid (ZA) at clinically relevant doses is active against tumours not located in bone. Mice transgenic for the activated ErbB-2 oncogene were treated with a cumulative number of doses equivalent to that recommended in human beings. A significant increase in tumour-free and overall survival was observed in mice treated with ZA. At clinically compatible concentrations, ZA modulated the mevalonate pathway and affected protein prenylation in both tumour cells and macrophages. A marked reduction in the number of tumour-associated macrophages was paralleled by a significant decrease in tumour vascularization. The local production of vascular endothelial growth factor and interleukin-10 was drastically down-regulated in favour of interferon-γ production. Peritoneal macrophages and tumour-associated macrophages of ZA-treated mice recovered a full M1 antitumoral phenotype, as shown by nuclear translocation of nuclear factor kB, inducible nitric oxide synthase expression and nitric oxide production. These data indicate that clinically achievable doses of ZA inhibit spontaneous mammary cancerogenesis by targeting the local microenvironment, as shown by a decreased tumour vascularization, a reduced number of tumour-associated macrophages and their reverted polarization from M2 to M1 phenotype.
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DOI：
10.1093/jnci/djk054
发表时间：
2007-02-21
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
Daubine, Florence;Le Gall, Celine;Clezardin, Philippe
通讯作者：
Clezardin, Philippe
影响因子：
15.9
作者：
Ghigo, D;Aldieri, E;Bosia, A
通讯作者：
Bosia, A
影响因子：
45.3
作者：
Kyle, Robert A.;Yee, Gary C.;Anderson, Kenneth
通讯作者：
Anderson, Kenneth
影响因子：
10.4
作者：
Hasmim, M.;Bieler, G.;Rueegg, C.
通讯作者：
Rueegg, C.
影响因子：
5.6
作者：
Caraglia, Michele;Marra, Monica;Abbruzzese, Alberto
通讯作者：
Abbruzzese, Alberto