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Rapid induction of pancreatic cancer cells to cancer stem cells via heterochromatin modulation

机译:通过异铬胺调节快速诱导胰腺癌细胞对癌症干细胞的诱导

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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 4days in inducing medium (mTeSR containing FBS, B27, MEK inhibitor, GSK3 inhibitor, and VPA), and another 2days 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.
机译:安装证据支持CSCs(癌症干细胞)在癌症复发中起着至关重要的作用。因此,消除CSCs目前被认为是完全缓解的重要治疗策略。 CSC研究中的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铬胺调制来诱导块状胰腺癌细胞对CSC的方法。在诱导培养基(MTESR,B27,MEK抑制剂,GSK3抑制剂和VPA中,将两个胰腺癌细胞系PANC1和BXPC3培养为4天,并且在球形培养基中进行另外2天(补充B27的MTESR)。然后将诱导的细胞分离成单细胞并在球形培养基中悬浮培养。结果发现大多数诱导细胞形成的球体,其可以生长较大并且连续传代。 Panc1球体的表征证明球形细胞表达增加的胰腺癌干细胞表面标志物和干细胞基因,更耐化疗,并且在体内更加致瘤,表明诱导的球体细胞获得CSC性质。因此,我们开发的诱导方法可用于获得来自癌细胞的足够数量的CSC,并有助于CSC靶向治疗的研究。

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