Human Pancreatic Cancer Stem Cells: Implications for How We Treat Pancreatic Cancer
Human Pancreatic Cancer Stem Cells: Implications for How We Treat Pancreatic Cancer
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DOI：
10.1593/tlo.08013
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发表时间：
2008-03-01
影响因子：
5
通讯作者：
Simeone, Diane M.
中科院分区：
文献类型：
--
作者：
Lee, Cheong J.;Li, Chenwei;Simeone, Diane M.
胰腺癌是所有主要恶性肿瘤中预后最差的，其年死亡率接近年发病率。延误诊断，相对化疗和放射抵抗和内在的生物侵略性都有助于与胰腺癌相关的预后差。寻找胰腺癌有效疗法的令人沮丧的努力的答案可能通过对肿瘤发生的新观点来获得，肿瘤发生是由被称为癌症干细胞（CSC）的选定细胞群控制的过程。癌症干细胞与正常干细胞一样，具有自我更新和多谱系分化的特性，并具有固有的增强的DNA损伤反应和修复机制，使其难以根除。最初在白血病中发现，研究人员已经在几种实体器官恶性肿瘤中发现了CSC，包括乳腺癌，脑癌，前列腺癌和结肠癌。我们最近在人类胰腺癌中发现了CSC群体。这些胰腺CSC占所有胰腺癌细胞的0.5%至1.0%，并表达细胞表面标志物CD44、CD24和上皮特异性抗原。胰腺CSC已被证明对标准化疗和放疗具有抗性，并且可能需要设计针对这种独特细胞群的特定疗法来确定治疗这种令人沮丧的疾病的有效疗法。
Pancreatic cancer has the worst prognosis of any major malignancy, with an annual death rate that approximates the annual incidence rate. Delayed diagnosis, relative chemotherapy and radiation resistance and an intrinsic biologic aggressiveness all contribute to the abysmal prognosis associated with pancreatic cancer. Answers to the frustrating effort to find effective therapies for pancreatic cancer may be gained through a renewed perspective on tumorigenesis as a process governed by a select population of cells, termed cancer stem cells (CSCs). Cancer stem cells, like their normal counterparts, have the properties of self-renewal and multilineage differentiation and possess inherently heightened DNA damage response and repair mechanisms that make them difficult to eradicate. Initially discovered in leukemias, researchers have identified CSCs in several solid-organ malignancies including breast, brain, prostate, and colon cancers. We have recently identified a CSC population in human pancreatic cancers. These pancreatic CSC represent 0.5% to 1.0% of all pancreatic cancer cells and express the cell surface markers CD44, CD24, and epithelial-specific antigen. Pancreatic CSCs have been shown to be resistant to standard chemotherapy and radiation, and devising specific therapies to target this distinct cell population is likely needed to identify effective therapies to treat this dismal disease.