Castellanos Jason A, Merchant Nipun B, Nagathihalli Nagaraj S
Department of Surgery, Vanderbilt University School of Medicine, Nashville, TN, USA.
Onco Targets Ther. 2013 Sep 13;6:1261-7. doi: 10.2147/OTT.S34670.
Pancreatic ductal adenocarcinoma is one of the most aggressive solid malignancies and is characterized by poor response to current therapy and a dismal survival rate. Recent insights regarding the role of cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT) in tumorigenesis have brought further understanding to the field and have highlighted new therapeutic targets. CSCs are a distinct subset of cancer cells, with the ability to differentiate into other cell types and self-renew in order to fuel the maintenance of tumor amplification. Transition of a cancer cell from an EMT leads to increased migratory and invasive properties, and thus facilitates initiation of metastasis. EMT is regulated by a complex network of factors that includes cytokines, growth factors, aberrant signaling pathways, transcription factors, and the tumor microenvironment. There is emerging evidence that the EMT process may give rise to CSCs, or at least cells with stem cell-like properties. We review the key pathways involved in both of these processes, the biomarkers used to identify CSCs, and new therapeutic approaches targeting CSCs and EMT in pancreatic ductal adenocarcinoma.
胰腺导管腺癌是最具侵袭性的实体恶性肿瘤之一，其特点是对当前治疗反应不佳且生存率极低。最近关于癌症干细胞（CSCs）和上皮-间质转化（EMT）在肿瘤发生中的作用的见解为该领域带来了进一步的认识，并突出了新的治疗靶点。癌症干细胞是癌细胞的一个独特亚群，具有分化为其他细胞类型和自我更新的能力，以维持肿瘤的扩增。癌细胞从上皮-间质转化会导致迁移和侵袭特性增加，从而促进转移的起始。上皮-间质转化受包括细胞因子、生长因子、异常信号通路、转录因子和肿瘤微环境在内的复杂因子网络调控。越来越多的证据表明，上皮-间质转化过程可能产生癌症干细胞，或至少产生具有干细胞样特性的细胞。我们综述了这两个过程中涉及的关键途径、用于识别癌症干细胞的生物标志物，以及针对胰腺导管腺癌中癌症干细胞和上皮-间质转化的新治疗方法。
