Cancer associated fibroblasts have phenotypic and functional characteristics similar to the fibrocytes that represent a novel MDSC subset
Cancer associated fibroblasts have phenotypic and functional characteristics similar to the fibrocytes that represent a novel MDSC subset
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DOI：
10.1080/2162402x.2015.1034918
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发表时间：
2015-01-01
期刊：
影响因子：
7.2
通讯作者：
Guc, Dicle
中科院分区：
文献类型：
--
作者：
Gunaydin, Gurcan;Kesikli, S. Altug;Guc, Dicle
循环纤维细胞是一种新的髓源性抑制细胞（MDSC）亚群，也被认为参与了肿瘤免疫逃逸。这种新的纤维细胞亚群具有类似于非单核细胞MDSC（CD 14（-）CD 11 c（hi）CD 123（-））的表面表型，并表现出免疫调节作用。纤维细胞（循环成纤维细胞-祖细胞）的大多数效应子功能是作为组织成纤维细胞完成的，同样在肿瘤微环境中。因此，应评估肿瘤组织中的成纤维细胞是否表现出与血源性纤维细胞相似的分子/基因表达模式和功能作用。利用化学诱导的大鼠乳腺癌模型获得癌相关成纤维细胞（CAFs）。CAF和正常组织成纤维细胞（NF）分别从癌性和健康乳腺组织中分离，使用先前描述的酶促方案。通过流式细胞术分析CAF和NF的细胞表面表型，并通过基因集富集分析（GSEA）分析基因表达谱。将PBMC与NF或CAF共培养，并通过CFSE测定评估PBMC的增殖。波形蛋白免疫细胞化学染色进行形态学分析。CAF是纺锤形细胞，与血液传播的细胞不同。它们不表达CD 80，并且它们的MHC-II表达低于NF。虽然CAFs表达髓样标志物CD 11b/c，但其表达低于循环纤维细胞。CAFs不表达粒细胞/嗜中性粒细胞标记物，它们似乎在含有T（HELPER）2样细胞因子的环境中发育。它们还表现出与血液传播的同类物相似的免疫抑制作用。总之，CAF显示出与循环纤维细胞相似的表型和功能特征，据报道，循环纤维细胞代表了独特的MDSC亚群。
Circulating fibrocytes were reported to represent a novel myeloid-derived suppressor cell (MDSC) subset and they were also proposed to be involved in the tumor immune escape. This novel fibrocyte subset had a surface phenotype resembling non-monocytic MDSCs (CD14(-)CD11c(hi)CD123(-)) and exhibited immunomodulatory roles. Most effector functions of fibrocytes (circulating fibroblast-progenitors) are accomplished as tissue fibroblasts, likewise in the tumor microenvironment. Therefore, fibroblasts at tumor tissues should be evaluated whether they display similar molecular/gene expression patterns and functional roles to the blood-borne fibrocytes. A chemically induced rat breast carcinogenesis model was utilized to obtain cancer associated fibroblasts (CAFs). CAFs and normal tissue fibroblasts (NFs) were isolated from cancerous and healthy breast tissues, respectively, using a previously described enzymatic protocol. Both CAFs and NFs were analyzed for cell surface phenotypes by flow cytometry and for gene expression profiles by gene set enrichment analysis (GSEA). PBMCs were cocultured with either NFs or CAFs and proliferations of PBMCs were assessed by CFSE assays. Morphological analyses were performed by immunocytochemistry stainings with vimentin. CAFs were spindle shaped cells unlike their blood-borne counterparts. They did not express CD80 and their MHC-II expression was lower than NFs. Although CAFs expressed the myeloid marker CD11b/c, its expression was lower than that on the circulating fibrocytes. CAFs did not express granulocytic/neutrophilic markers and they seemed to have developed in an environment containing T(HELPER)2-like cytokines. They also showed immunosuppressive effects similar to their blood-borne counterparts. In summary, CAFs showed similar phenotypic and functional characteristics to the circulating fibrocytes that were reported to represent a unique MDSC subset.