Lima Luize G, Chammas Roger, Monteiro Robson Q, Moreira Maria Elisabete C, Barcinski Marcello A
Division of Experimental Medicine, National Cancer Institute, RJ, Brazil; Institute of Medical Biochemistry, Federal University of Rio de Janeiro, RJ, Brazil.
Cancer Lett. 2009 Oct 8;283(2):168-75. doi: 10.1016/j.canlet.2009.03.041. Epub 2009 Apr 28.
Exposure of phosphatidylserine (PS) on cellular membranes and membrane-derived microvesicles stimulates a number of anti-inflammatory responses involved in malignant processes. Herein we show that B16F10 cells, a highly metastatic melanoma cell line, produce large quantities of PS-containing microvesicles in vitro. Tumor microvesicles increased TGF-beta(1) production by cultured macrophages and, in vivo, enhanced the metastatic potential of B16F10 cells in C57BL/6 mice, both effects being reversed by annexin V. Most strikingly, microvesicles induced melanoma metastasis in BALB/c mice, which are normally resistant to this tumor cell line. Altogether, this is the first demonstration that tumor-derived microvesicles favor the establishment of melanoma metastasis in a PS-dependent manner, possibly by down-regulating the host's inflammatory and/or anti-tumoral immune responses.
细胞膜和膜衍生微泡上磷脂酰丝氨酸（PS）的暴露会刺激许多参与恶性过程的抗炎反应。在此我们表明，B16F10细胞，一种高转移性黑色素瘤细胞系，在体外产生大量含PS的微泡。肿瘤微泡增加了培养的巨噬细胞中转化生长因子-β1（TGF-β1）的产生，并且在体内增强了B16F10细胞在C57BL/6小鼠中的转移潜力，这两种效应均被膜联蛋白V逆转。最引人注目的是，微泡在通常对该肿瘤细胞系具有抗性的BALB/c小鼠中诱导黑色素瘤转移。总之，这是首次证明肿瘤衍生的微泡以PS依赖的方式促进黑色素瘤转移的建立，可能是通过下调宿主的炎症和/或抗肿瘤免疫反应。
