Tumour-derived microvesicles modulate biological activity of human monocytes
Tumour-derived microvesicles modulate biological activity of human monocytes
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DOI：
10.1016/j.imlet.2007.07.014
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发表时间：
2007-11-15
影响因子：
4.4
通讯作者：
Zembala, Marek
中科院分区：
文献类型：
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作者：
Baj-Krzyworzeka, Monika;Szatanek, Rafal;Zembala, Marek
肿瘤细胞脱落的膜碎片（肿瘤源性微囊，TMV）可能与免疫系统细胞相互作用。我们之前的观察表明，TMV携带肿瘤细胞的几种表面决定因子和mRNA，并将其中一些转移到单核细胞。本研究确定了TMV对作为肿瘤浸润性巨噬细胞（TIM）前体的人单核细胞生物活性的影响。发现TMV激活单核细胞，表现为HLA-DR表达增加，诱导ROI（活性氧中间体）的产生以及肿瘤坏死因子（TNF）、白细胞介素(IL)- 10、IL- 12p40 mRNA的积累和分泌。TNF合成的诱导依赖于CD44，因为CD44对单核细胞的阻断使其分泌消失。tmv处理的单核细胞显示出增强的抗肿瘤活性，这是通过体外对肿瘤细胞增强的细胞毒性/细胞抑制来判断的。综上所述，这些结果表明，TMV显著调节单核细胞的生物活性，从而模仿肿瘤细胞对它们的作用。这可能表明肿瘤细胞与TIM不仅通过直接接触、可溶性因子，还通过TMV相互作用。(C) 2007 Elsevier b.v.。版权所有。
Tumour cells are shedding membrane fragments (tumour-derived microvesicles, TMV) that may interact with cells of immune system. Our previous observations indicated that TMV carry several surface determinants and mRNA of tumour cells and transfer some of them to monocytes. This study determined the effect of TMV on biological activity of human monocytes as the precursors of tumour infiltrating macrophages (TIM). It was found that TMV activated monocytes as shown by an increased HLA-DR expression, induced production of ROI (reactive oxygen inter-mediates) and of tumour necrosis factor (TNF), interleukin (IL)- 10, IL- 12p40 accumulation of mRNA and their secretion. Induction of TNF synthesis was CD44 dependent as blocking of CD44 on monocytes abolished its secretion. TMV-treated monocytes showed an increased antitumour activity as judged by enhanced cytotoxicity/cytostasis against tumour cells in vitro. Taken together, these results indicate that TMV significantly modulate biological activity of monocytes and thus mimic the effect of tumour cells on them. This may suggest that tumour cells interact with TIM not only via direct contact, soluble factors, but also TMV. (C) 2007 Elsevier B.V.. All rights reserved.