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Gamma-smooth muscle actin expression is associated with epithelial-mesenchymal transition and stem-like properties in hepatocellular carcinoma.

Benzoubir N, Mussini C, Lejamtel C, Dos Santos A, Guillaume C, Desterke C, Samuel D, Bréchot C, Bourgeade MF, Guettier C - PLoS ONE (2015)

Bottom Line: Interestingly, this expression was significantly correlated with poor tumour differentiation and progenitor cell features characterized by the expression of EpCAM and K19.Taken 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.

View Article: PubMed Central - PubMed

Affiliation: Inserm, Unité 785, Villejuif, F-94800, France; Univ Paris-Sud, UMR-S 785, Villejuif, F-94800, France; DHU Hepatinov, Villejuif, France.

ABSTRACT

Background and aims: The 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.

Methods: The 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.

Results: We 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.

Conclusion: Taken 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.

No MeSH data available.


Related in: MedlinePlus

Odds ratio meta-analyses of data from 58 HCC nodules.Meta-analyses were performed on clinical and biological criteria.
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pone.0130559.g005: Odds ratio meta-analyses of data from 58 HCC nodules.Meta-analyses were performed on clinical and biological criteria.

Mentions: Meta-analyses of these 58 HCC nodules from adult patients indicated that γSMA expression was not correlated to age, type of surgery (liver transplantation or resection), tumour necrosis or neoadjuvant TACE treatment (Table 1 and Fig 5). By contrast, in the context of adult HCC, γSMA expression was significantly associated with a poor degree of tumour differentiation. In line with this finding, the majority of paediatric HCC cases were classified as Edmondson 3.


Gamma-smooth muscle actin expression is associated with epithelial-mesenchymal transition and stem-like properties in hepatocellular carcinoma.

Benzoubir N, Mussini C, Lejamtel C, Dos Santos A, Guillaume C, Desterke C, Samuel D, Bréchot C, Bourgeade MF, Guettier C - PLoS ONE (2015)

Odds ratio meta-analyses of data from 58 HCC nodules.Meta-analyses were performed on clinical and biological criteria.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4482489&req=5

pone.0130559.g005: Odds ratio meta-analyses of data from 58 HCC nodules.Meta-analyses were performed on clinical and biological criteria.
Mentions: Meta-analyses of these 58 HCC nodules from adult patients indicated that γSMA expression was not correlated to age, type of surgery (liver transplantation or resection), tumour necrosis or neoadjuvant TACE treatment (Table 1 and Fig 5). By contrast, in the context of adult HCC, γSMA expression was significantly associated with a poor degree of tumour differentiation. In line with this finding, the majority of paediatric HCC cases were classified as Edmondson 3.

Bottom Line: Interestingly, this expression was significantly correlated with poor tumour differentiation and progenitor cell features characterized by the expression of EpCAM and K19.Taken 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.

View Article: PubMed Central - PubMed

Affiliation: Inserm, Unité 785, Villejuif, F-94800, France; Univ Paris-Sud, UMR-S 785, Villejuif, F-94800, France; DHU Hepatinov, Villejuif, France.

ABSTRACT

Background and aims: The 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.

Methods: The 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.

Results: We 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.

Conclusion: Taken 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.

No MeSH data available.


Related in: MedlinePlus