Tumor budding cells, cancer stem cells and epithelial-mesenchymal transition-type cells in pancreatic cancer.
Tumor budding cells, cancer stem cells and epithelial-mesenchymal transition-type cells in pancreatic cancer.
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DOI：
10.3389/fonc.2012.00209
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发表时间：
2012
影响因子：
4.7
通讯作者：
Karamitopoulou E
中科院分区：
文献类型：
--
作者：
Karamitopoulou E
胰腺导管腺癌（PDAC）是最致命的癌症之一，5年生存率低于5%。此外，PDAC 无法及早发现并抵制治疗。已知 PDAC 中会发生多种遗传改变组合，包括 KRAS 突变激活、p16/CDKN2A 和 SMAD4 (DPC4) 失活以及 PTEN/PI3K/AKT 信号传导失调。通过与 Wingless-INT 通路的相互作用，这些通路的下游分子参与了上皮间质转化 (EMT) 的促进。新的证据表明，癌症干细胞 (CSC)（已在 PDAC 中发现了一小群）和 EMT 型细胞在胰腺癌的耐药性、侵袭和转移中发挥着关键作用。 EMT在组织学上可能以肿瘤出芽的存在为代表，肿瘤出芽被描述为在胃肠道癌（包括结直肠癌、食管癌、胃癌和壶腹癌）的侵袭性前沿出现单个肿瘤细胞或小簇（<5）去分化细胞，并且与不良预后相关。最近显示，肿瘤出芽在 PDAC 中频繁发生，并与不良临床病理特征以及无病生存率和总生存率降低相关。本综述的目的是对形态学和分子方面进行简短概述，强调 PDAC 中肿瘤出芽细胞、CSC 和 EMT 型细胞之间的关系。
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with a 5-year survival rate of less than 5%. Moreover, PDAC escapes early detection and resists treatment. Multiple combinations of genetic alterations are known to occur in PDAC including mutational activation of KRAS, inactivation of p16/CDKN2A and SMAD4 (DPC4) and dysregulation of PTEN/PI3K/AKT signaling. Through their interaction with Wingless-INT pathway, the downstream molecules of these pathways have been implicated in the promotion of epithelial–mesenchymal transition (EMT). Emerging evidence has demonstrated that cancer stem cells (CSCs), small populations of which have been identified in PDAC, and EMT-type cells play critical roles in drug resistance, invasion, and metastasis in pancreatic cancer. EMT may be histologically represented by the presence of tumor budding which is described as the occurrence of single tumor cells or small clusters (<5) of dedifferentiated cells at the invasive front of gastrointestinal (including colorectal, oesophageal, gastric, and ampullary) carcinomas and is linked to poor prognosis. Tumor budding has recently been shown to occur frequently in PDAC and to be associated with adverse clinicopathological features and decreased disease-free and overall survival. The aim of this review is to present a short overview on the morphological and molecular aspects that underline the relationship between tumor budding cells, CSCs, and EMT-type cells in PDAC.