Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden.
Sci Rep. 2016 Aug 23;6:31805. doi: 10.1038/srep31805.
Accumulating data indicates that tumor-derived extracellular vesicles (EVs) are responsible for tumor-promoting effects. However, if tumor EVs also prepare the tumor-bearing organ for subsequent tumor growth, and if this effect is different in low and high malignant tumors is not thoroughly explored. Here we used orthotopic rat Dunning R-3327 prostate tumors to compare the role of EVs from fast growing and metastatic MatLyLu (MLL) tumors with EVs from more indolent and non-metastatic Dunning G (G) tumors. Prostate tissue pre-conditioned with MLL-EVs in vivo facilitated G tumor establishment compared to G-EVs. MLL-EVs increased prostate epithelial proliferation and macrophage infiltration into the prostate compared to G-EVs. Both types of EVs increased macrophage endocytosis and the mRNA expression of genes associated with M2 polarization in vitro, with MLL-EVs giving the most pronounced effects. MLL-EVs also altered the mRNA expression of growth factors and cytokines in primary rat prostate fibroblasts compared to G-EVs, suggesting fibroblast activation. Our findings propose that EVs from metastatic tumors have the ability to prime the prostate tissue and enhance tumor growth to a higher extent than EVs from non-metastatic tumors. Identifying these differences could lead to novel therapeutic targets and potential prognostic markers for prostate cancer.
越来越多的数据表明，肿瘤来源的细胞外囊泡（EVs）是促进肿瘤生长的原因。然而，如果肿瘤 EVs 也为肿瘤生长的后续阶段准备肿瘤所在的器官，以及这种作用在低恶性和高恶性肿瘤之间是否存在差异，目前尚未得到深入研究。在这里，我们使用原位种植的大鼠 Dunning R-3327 前列腺肿瘤，比较了生长迅速且具有转移性的 MatLyLu（MLL）肿瘤来源的 EVs 与生长缓慢且无转移性的 Dunning G（G）肿瘤来源的 EVs 的作用。与 G-EVs 相比，体内预孵育 MLL-EVs 的前列腺组织更有利于 G 肿瘤的建立。与 G-EVs 相比，MLL-EVs 增加了前列腺上皮细胞的增殖和巨噬细胞浸润到前列腺。两种类型的 EVs 均增加了体外巨噬细胞的内吞作用和与 M2 极化相关的基因的 mRNA 表达，其中 MLL-EVs 的作用最为显著。与 G-EVs 相比，MLL-EVs 还改变了原代大鼠前列腺成纤维细胞中生长因子和细胞因子的 mRNA 表达，提示成纤维细胞的激活。我们的研究结果表明，转移性肿瘤来源的 EVs 具有使前列腺组织预致敏并增强肿瘤生长的能力，其程度高于非转移性肿瘤来源的 EVs。识别这些差异可能为前列腺癌提供新的治疗靶点和潜在的预后标志物。
