Macrophage traits in cancer cells are induced by macrophage-cancer cell fusion and cannot be explained by cellular interaction.
Macrophage traits in cancer cells are induced by macrophage-cancer cell fusion and cannot be explained by cellular interaction.
复制标题
DOI：
10.1186/s12885-015-1935-0
复制
发表时间：
2015-11-20
期刊：
影响因子：
3.8
通讯作者：
Lindström A
中科院分区：
文献类型：
--
作者：
Shabo I;Midtbö K;Andersson H;Åkerlund E;Olsson H;Wegman P;Gunnarsson C;Lindström A
细胞融合是正常发育和组织再生的自然过程。癌细胞和巨噬细胞之间的融合产生具有来自两种母体细胞的遗传和表型特征的转移性杂种。然而，在临床背景下没有用于检测细胞融合的临床标志物。巨噬细胞特异性抗原CD 163在乳腺癌和结直肠癌中的肿瘤细胞中的表达被报道，并被认为是由肿瘤间质中的巨噬细胞-癌细胞融合引起的。本研究的目的是检查细胞融合过程作为乳腺巨噬细胞表型的生物学解释。将从男性供血者收获的单核细胞活化为M2巨噬细胞，并在ThinCert transwell系统中与GFP标记的MCF-7癌细胞共培养。MCF 7/巨噬细胞杂交瘤通过自发细胞融合产生，通过荧光激活细胞分选分离，并通过荧光显微镜、短串联重复序列分析和流式细胞术确认。通过免疫组织化学方法评价了127名妇女乳腺肿瘤样本材料中CD 163的表达。MCF-7/巨噬细胞杂交体以2%的平均比率自发产生，并显示来自两种母体细胞的表型和遗传性状。MCF-7细胞中的CD 163表达不能通过与M2活化的巨噬细胞的旁分泌相互作用来诱导。肿瘤切片中的⑶ 163阳性癌细胞在克隆收集中生长，并且> 25%的阳性癌细胞的截止点与无病存活和总体存活显著相关。总之，乳腺癌中的巨噬细胞特征可能是由细胞融合引起的，而不是由旁分泌细胞相互作用解释的。这些数据为细胞融合在乳腺癌中的作用提供了新的见解，并有助于开发识别细胞融合的临床标志物。
Cell fusion is a natural process in normal development and tissue regeneration. Fusion between cancer cells and macrophages generates metastatic hybrids with genetic and phenotypic characteristics from both maternal cells. However, there are no clinical markers for detecting cell fusion in clinical context. Macrophage-specific antigen CD163 expression in tumor cells is reported in breast and colorectal cancers and proposed being caused by macrophages-cancer cell fusion in tumor stroma. The purpose of this study is to examine the cell fusion process as a biological explanation for macrophage phenotype in breast. Monocytes, harvested from male blood donor, were activated to M2 macrophages and co-cultured in ThinCert transwell system with GFP-labeled MCF-7 cancer cells. MCF7/macrophage hybrids were generated by spontaneous cell fusion, isolated by fluorescence-activated cell sorting and confirmed by fluorescence microscopy, short tandem repeats analysis and flow cytometry. CD163 expression was evaluated in breast tumor samples material from 127 women by immunohistochemistry. MCF-7/macrophage hybrids were generated spontaneously at average rate of 2 % and showed phenotypic and genetic traits from both maternal cells. CD163 expression in MCF-7 cells could not be induced by paracrine interaction with M2-activated macrophages. CD163 positive cancer cells in tumor sections grew in clonal collection and a cutoff point >25 % of positive cancer cells was significantly correlated to disease free and overall survival. In conclusion, macrophage traits in breast cancer might be caused by cell fusion rather than explained by paracrine cellular interaction. These data provide new insights into the role of cell fusion in breast cancer and contributes to the development of clinical markers to identify cell fusion.