a Medical Research Center, Beijing Chaoyang Hospital , Capital Medical University , Beijing , China.
Cell Cycle. 2018;17(12):1487-1495. doi: 10.1080/15384101.2018.1489180. Epub 2018 Jul 25.
Mounting evidence supports that CSCs (cancer stem cells) play a vital role in cancer recurrence. Therefore elimination of CSCs is currently considered to be an important therapeutic strategy for complete remission. A major obstacle in CSC research is the obtainment of sufficient numbers of functional CSC populations. Here, we established a method to induce bulk pancreatic cancer cells to CSCs via heterochromatin modulation. Two pancreatic cancer cell lines Panc1 and Bxpc3 were cultured for 4 days in inducing medium (mTeSR containing FBS, B27, MEK inhibitor, GSK3 inhibitor, and VPA), and another 2 days in sphere culture medium (mTeSR supplemented with B27). Then the induced cells were dissociated into single cells and cultured in suspension in sphere culture medium. It was found that the majority of induced cells formed spheres which could grow larger and be passaged serially. Characterization of Panc1 sphere cells demonstrated that the sphere cells expressed increased pancreatic cancer stem cell surface markers and stem cell genes, were more resistant to chemotherapy, and were more tumorigenic in vivo, indicating that the induced sphere cells acquired CSC properties. Thus, the inducing method we developed may be used to obtain a sufficient number of CSCs from cancer cells, and contribute to the research for CSC-targeting therapy.
越来越多的证据支持癌症干细胞 (CSC) 在癌症复发中起着至关重要的作用。因此，消除 CSC 目前被认为是完全缓解的重要治疗策略。CSC 研究的一个主要障碍是获得足够数量的功能性 CSC 群体。在这里，我们建立了一种通过异染色质调节诱导大量胰腺癌细胞成为 CSC 的方法。将两种胰腺癌细胞系 Panc1 和 Bxpc3 在诱导培养基（含 FBS、B27、MEK 抑制剂、GSK3 抑制剂和 VPA 的 mTeSR）中培养 4 天，然后在球体培养基（补充有 B27 的 mTeSR）中培养 2 天。然后将诱导的细胞解离成单细胞并在球体培养基的悬浮液中培养。结果发现，大多数诱导的细胞形成了球体，这些球体可以生长得更大并连续传代。对 Panc1 球体细胞的特征分析表明，球体细胞表达了增加的胰腺癌症干细胞表面标志物和干细胞基因，对化疗的抵抗力更强，在体内的致瘤性更强，表明诱导的球体细胞获得了 CSC 特性。因此，我们开发的诱导方法可用于从癌细胞中获得足够数量的 CSC，并有助于 CSC 靶向治疗的研究。
