Baj-Krzyworzeka Monika, Szatanek Rafał, Weglarczyk Kazimierz, Baran Jarosław, Zembala Marek
Department of Clinical Immunology, Polish-American Institute of Paediatrics, Jagiellonian University Medical College, Wielicka 265 Str., 30-663 Cracow, Poland.
Immunol Lett. 2007 Nov 15;113(2):76-82. doi: 10.1016/j.imlet.2007.07.014. Epub 2007 Aug 22.
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 intermediates) 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.
肿瘤细胞会脱落膜碎片（肿瘤衍生微泡，TMV），这些微泡可能与免疫系统细胞相互作用。我们之前的观察表明，TMV携带肿瘤细胞的多种表面决定簇和mRNA，并将其中一些传递给单核细胞。本研究确定了TMV对作为肿瘤浸润巨噬细胞（TIM）前体的人单核细胞生物学活性的影响。结果发现，TMV可激活单核细胞，表现为HLA-DR表达增加、活性氧中间体（ROI）以及肿瘤坏死因子（TNF）、白细胞介素（IL）-10、IL-12p40的产生增加，mRNA积累及其分泌增加。TNF合成的诱导依赖于CD44，因为阻断单核细胞上的CD44可消除其分泌。通过体外对肿瘤细胞增强的细胞毒性/细胞生长抑制作用判断，经TMV处理的单核细胞显示出增强的抗肿瘤活性。综上所述，这些结果表明TMV可显著调节单核细胞的生物学活性，从而模拟肿瘤细胞对它们的作用。这可能提示肿瘤细胞与TIM的相互作用不仅通过直接接触、可溶性因子，还通过TMV。
