Epithelial-to-Mesenchymal Transition and Cancer Invasiveness: What Can We Learn from Cholangiocarcinoma?
Epithelial-to-Mesenchymal Transition and Cancer Invasiveness: What Can We Learn from Cholangiocarcinoma?
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DOI：
10.3390/jcm4121958
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发表时间：
2015-12-19
影响因子：
3.9
通讯作者：
Strazzabosco M
中科院分区：
文献类型：
--
作者：
Brivio S;Cadamuro M;Fabris L;Strazzabosco M
除了在胚胎发育中已被证实的作用外，上皮向间充质转化(EMT)已被认为是几种上皮性恶性肿瘤中有利于肿瘤转移的一般机制。在此，我们回顾了胆管癌(CCA)中EMT的主题，CCA是一种起源于胆管衬里上皮细胞(胆管细胞)的原发性肝癌，其特点是有丰富的间质反应。由于明显的侵袭性和治疗机会的稀少，CCA的预后令人沮丧。在CCA中，一些报告表明癌细胞获得了许多EMT生物标志物和功能。这些表型变化可能是由肿瘤微环境中释放的自分泌和旁分泌信号(细胞因子、生长因子、形态因子)和细胞内刺激(microRNAs、癌基因、肿瘤抑制基因)引起的，这些刺激与特定的疾病机制有关，包括慢性炎症和缺氧。然而，缺乏证据支持肿瘤胆管细胞向间质细胞的完整EMT，而CCA细胞获得EMT样变化更反映了向增强的前侵袭性表型的转变，这可能是由肿瘤间质诱导的。这一概念可能有助于识别早期转移行为的新生物标记物以及潜在的治疗靶点。
In addition to its well-established role in embryo development, epithelial-to-mesenchymal transition (EMT) has been proposed as a general mechanism favoring tumor metastatization in several epithelial malignancies. Herein, we review the topic of EMT in cholangiocarcinoma (CCA), a primary liver cancer arising from the epithelial cells lining the bile ducts (cholangiocytes) and characterized by an abundant stromal reaction. CCA carries a dismal prognosis, owing to a pronounced invasiveness and scarce therapeutic opportunities. In CCA, several reports indicate that cancer cells acquire a number of EMT biomarkers and functions. These phenotypic changes are likely induced by both autocrine and paracrine signals released in the tumor microenvironment (cytokines, growth factors, morphogens) and intracellular stimuli (microRNAs, oncogenes, tumor suppressor genes) variably associated with specific disease mechanisms, including chronic inflammation and hypoxia. Nevertheless, evidence supporting a complete EMT of neoplastic cholangiocytes into stromal cells is lacking, and the gain of EMT-like changes by CCA cells rather reflects a shift towards an enhanced pro-invasive phenotype, likely induced by the tumor stroma. This concept may help to identify new biomarkers of early metastatic behavior along with potential therapeutic targets.