Characterization of tumor-derived mesenchymal stem cells potentially differentiating into cancer-associated fibroblasts in lung cancer
Characterization of tumor-derived mesenchymal stem cells potentially differentiating into cancer-associated fibroblasts in lung cancer
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DOI：
10.1007/s12094-018-1894-4
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发表时间：
2018-12-01
影响因子：
3.4
通讯作者：
Orciani, M.
中科院分区：
文献类型：
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作者：
Arena, S.;Salati, M.;Orciani, M.
目的本研究的目的是了解从肺肿瘤组织（T-MSC）中分离的间充质干细胞（T-MSC）是否可以分化为癌症相关成纤维细胞（CAF），从而促进上皮实体瘤中的肿瘤进展、血管生成和转移，模拟肿瘤微环境的影响。方法从一名因肺腺癌接受肺叶切除术的患者的健康组织（对照，C-MSC）和肿瘤组织（T-MSC）中获取MSC。 pT1bN0。对分离的细胞进行分子标记的存在（通过分化肿瘤细胞的常规诊断表征进行鉴定）、干性特性和 CAF 相关标记表达。随后，将细胞与肺腺癌细胞系（A549细胞）共培养，以评估对增殖、癌基因表达和IL6分泌的影响。结果与肿瘤组织不同，C-和T-MSC不呈现EGFR突变，并表现出干细胞样免疫表型，其特征在于能够分化为骨、软骨和脂肪形成谱系。 T-MSC 中 CAF 相关标志物（-SMA、HI-1、MMP11、VEGF、CXCL12、TGF-1、TGF-RII、IL6、TNF）的表达显着高于 C-MSC。与 A549 细胞共培养导致 T-MSC 中选定癌基因的过度表达以及 IL6 分泌的增加，但 C-MSC 中却没有增加。 结论 与从健康组织中分离的 MSC 相比，从肿瘤组织中分离的 MSC 表现出不同的特性，表明在肿瘤微环境的影响下，T-MSC 向 CAF 相关表型分化。
PurposeThe goal of this study was to understand if mesenchymal stem cells isolated from lung tumor tissue (T-MSCs) may differentiate into cancer associated fibroblasts (CAFs), that promote neoplastic progression, angiogenesis and metastasis in the epithelial solid tumors, mimicking the tumor microenvironmental influence.MethodsMSCs were been obtained from healthy (Control, C-MSCs) and tumor (T-MSCs) tissue of one patient who underwent a lobectomy for a lung adenocarcinoma pT1bN0. Isolated cells were characterized for the presence of molecular markers (identified by routine diagnostic characterization in differentiated tumoral cells), stemness properties, and CAF-related markers expression. Subsequently, cells were co-cultured with a lung adenocarcinoma cell line (A549 cells) to evaluate the effects on proliferation, oncogene expression and IL6 secretion.ResultsC- and T-MSCs did not present EGFR mutations unlike tumor tissue and showed a stem-like immunophenotype, characterized by the ability to differentiate towards osteo-, chondro- and adipogenic lineages. The expression of markers referred to CAFs (-SMA, HI-1, MMP11, VEGF, CXCL12, TGF-1, TGF-RII, IL6, TNF) was significantly higher in T-MSCs than in C-MSCs. The co-cultures with A549 cells led to the over-expression of selected oncogenes and to the increase of IL6 secretion in T-MSCs but not in C-MSCs.ConclusionsMSCs isolated from tumor tissue displayed distinct properties compared to MSCs isolated from healthy tissue, suggesting T-MSCs differentiation towards a CAF-related phenotype under the influence of the tumoral microenvironment.