Abstract
Background and AimsThe prognosis of hepatocellular carcinoma (HCC) is hampered by frequent tumour recurrence and metastases. Epithelial-Mesenchymal Transition (EMT) is now recognized as a key process in tumour invasion, metastasis and the generation of cancer initiating cells. The morphological identification of EMT in tumour samples from the expression of novel mesenchymal markers could provide relevant prognostic information and aid in understanding the metastatic process.MethodsThe expression of Smooth Muscle Actins was studied using immunofluorescence and immunohistochemistry assays in cultured liver cells during an induced EMT process and in liver specimens from adult and paediatric HCC series.ResultsWe report here that in HCC cell lines treated with TGF-β and in HCC specimens, the expression of αSMA, a known mesenchymal marker of EMT, could never be detected. In addition, our in vitro studies identified the enteric form of SMA, γSMA, as being a marker of EMT. Moreover, this SMA isoform was expressed in 46% of 58 tumours from 42 adult HCC patients and in 90% of 16 tumours from 12 paediatric HCC patients. Interestingly, this expression was significantly correlated with poor tumour differentiation and progenitor cell features characterized by the expression of EpCAM and K19.ConclusionTaken together, our results support the conclusion that γSMA expression in HCC is strongly correlated with the EMT process, HCC aggressiveness and the identification of cancer stem cells. This correlation suggests that γSMA represents a novel and powerful marker to predict HCC progression.
Highlights
Hepatocellular carcinoma (HCC) is a major health problem in that it is the fifth most common cancer in the world and the third most frequent cause of cancer-related deaths
We report here that in hepatocellular carcinoma (HCC) cell lines treated with TGF-β and in HCC specimens, the expression of αSMA, a known mesenchymal marker of Epithelial-Mesenchymal Transition (EMT), could never be detected
Our results support the conclusion that γSMA expression in HCC is strongly correlated with the EMT process, HCC aggressiveness and the identification of cancer stem cells
Summary
Hepatocellular carcinoma (HCC) is a major health problem in that it is the fifth most common cancer in the world and the third most frequent cause of cancer-related deaths. Partial liver resection and liver transplantation have significantly improved survival with small tumours, the prognosis for HCC remains poor because of tumour invasiveness, frequent intrahepatic spread and extrahepatic metastases [2]. It has been suggested that epithelial to mesenchymal transition (EMT) might be closely associated with the acquisition of aggressive traits by tumour cells, facilitating the early stages of metastasis and the subsequent dissemination of carcinoma cells [3] [4]. The prognosis of hepatocellular carcinoma (HCC) is hampered by frequent tumour recurrence and metastases. Epithelial-Mesenchymal Transition (EMT) is recognized as a key process in tumour invasion, metastasis and the generation of cancer initiating cells. The morphological identification of EMT in tumour samples from the expression of novel mesenchymal markers could provide relevant prognostic information and aid in understanding the metastatic process
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