Role of epithelial-mesenchymal transition in pancreatic ductal adenocarcinoma: is tumor budding the missing link?
Role of epithelial-mesenchymal transition in pancreatic ductal adenocarcinoma: is tumor budding the missing link?
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DOI：
10.3389/fonc.2013.00221
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发表时间：
2013-09-17
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）是第四大常见的癌症死亡原因，其发病率在全球范围内呈上升趋势。对于所有阶段，5年生存率<5%。胰腺癌的致命性归因于其向淋巴系统和远端器官的高转移潜力。缺乏有效的治疗方案导致PDAC的高死亡率。近年来的研究表明，上皮-间质转化（EMT）在PDAC的疾病进展和耐药发生中起重要作用。肿瘤出芽被认为反映了EMT的过程，EMT允许肿瘤上皮细胞获得间充质表型，从而增加它们的迁移和侵袭能力，并帮助它们对凋亡信号产生抗性。在我们自己的小组最近的一项研究中，研究了PDAC中肿瘤出芽的存在和预后意义，并研究了PDAC中肿瘤出芽的高表达与PDAC的预后之间的关系。EMT表型靶点的鉴定可能有助于鉴定新的分子，以便将来针对它们的特异性治疗策略可能对肿瘤的预后产生潜在的影响。耐药性和侵袭性，从而改善PDAC患者的预后。这个简短的审查的目的是提出一个洞察EMT的形态学和分子方面的因素，参与诱导EMT在PDAC。
Pancreatic ductal adenocarcinoma (PDAC) ranks as the fourth commonest cause of cancer death while its incidence is increasing worldwide. For all stages, survival at 5 years is<5%. The lethal nature of pancreatic cancer is attributed to its high metastatic potential to the lymphatic system and distant organs. Lack of effective therapeutic options contributes to the high mortality rates of PDAC. Recent evidence suggests that epithelial-mesenchymal transition (EMT) plays an important role to the disease progression and development of drug resistance in PDAC. Tumor budding is thought to reflect the process of EMT which allows neoplastic epithelial cells to acquire a mesenchymal phenotype thus increasing their capacity for migration and invasion and help them become resistant to apoptotic signals. In a recent study by our own group the presence and prognostic significance of tumor budding in PDAC were investigated and an association between high-grade budding and aggressive clinicopathological features of the tumors as well as worse outcome of the patients was found. The identification of EMT phenotypic targets may help identifying new molecules so that future therapeutic strategies directed specifically against them could potentially have an impact on drug resistance and invasiveness and hence improve the prognosis of PDAC patients. The aim of this short review is to present an insight on the morphological and molecular aspects of EMT and on the factors that are involved in the induction of EMT in PDAC.