We previously demonstrated the conversion of normal stem cells, including induced pluripotent stem cells (iPSCs), into cancer stem cells (CSCs) without genetic manipulation. Herein, we designed a meta-analysis to assess gene expression profiles in different breast cancer cell lines focusing on the secretory factors responsible for conversion. As a result, fibroblast growth factor 2 (FGF2) was found to be the best candidate in T47D and BT549 cells, of which conditioned medium was previously successful in inducing CSCs. When treated with 3.1 μg/ml FGF2, mouse iPSCs not only maintained survival without LIF for three weeks but also acquired growth ability independent of FGF2. The resultant cells exhibited expression of stemness and cancer stem cell markers, sphere-forming ability, differentiation, and tumorigenicity with malignancy. The primary cultures of the tumor confirmed the signatures of CSCs with two different phenotypes with or without GFP expression under control of the Nanog promoter. Bioinformatic analysis of gene expression profiles suggested constitutive autocrine activation of the FGF receptor, integrins, focal adhesions, and PI3K/AKT pathways. FGF2 could potently initiate cancer as a component of the inflammatory microenvironment.

我们之前证明了正常干细胞，包括诱导多能干细胞 (iPSC)，无需基因操作即可转化为癌症干细胞 (CSC)。在此，我们设计了一项荟萃分析来评估不同乳腺癌细胞系中的基因表达谱，重点关注负责转化的分泌因子。结果，发现成纤维细胞生长因子 2 (FGF2) 是 T47D 和 BT549 细胞中的最佳候选者，其中条件培养基先前已成功诱导 CSC。当用 3.1 μg/ml FGF2 处理时，小鼠 iPSC 不仅可以在没有 LIF 的情况下存活三周，而且还获得了独立于 FGF2 的生长能力。所得细胞表现出干细胞和癌症干细胞标志物的表达、球体形成能力、分化和恶性肿瘤的致瘤性。肿瘤的原代培养证实了在 Nanog 启动子控制下具有或不具有 GFP 表达的两种不同表型的 CSC 的特征。基因表达谱的生物信息学分析表明 FGF 受体、整联蛋白、粘着斑和 PI3K/AKT 通路的组成型自分泌激活。FGF2 作为炎症微环境的一个组成部分可以有效地引发癌症。