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Hepatic stellate cells may relate to progression of intrahepatic cholangiocarcinoma
Annals of Surgical Oncology, 06/29/09
Hirohisa Okabe et al. – Study reports that stromal myofibroblasts may relate to the poor prognoses in intrahepatic cholangiocarcinoma (ICC) patients. Hepatic stellate (HS) cells appear to be involved in the progression of ICC.
Methods- Main objectives of this study were to:
- Assess the influence of myofibroblasts on the prognosis of ICC
- Identify HS cells in ICC stroma, and
- Investigate the interaction between HS cells (LI90 and LX-2) and ICC cells (HuCCT-1 and MEC) in vitro
- Association between α-smooth muscle actin (α-SMA) expression and the prognoses of 46 ICC pts after hepatic resection was evaluated by IHC analysis
- HS cells in myofibroblasts of ICC were identified using Abs for α-SMA, glial fibrillary acidic protein (GFAP), and desmin
- The influence of HS cells on the invasion and growth of ICC cells was examined in vitro using a coculture system
- Pts with high α-SMA expression exhibited the worse outcomes
- Multivariate analyses: high α-SMA expression and positivity for lymph-node metastasis were independent prognostic factors
- Because desmin- or GFAP-positive cells coexpressing α-SMA were observed in the ICC samples, they were considered to be derived from the HS cells
- On coculturing with HS cells, a remarkable increase was observed in the invasion and growth of the two ICC cell lines
Hideo Baba, 06/28/09
| Cross-talk between mesenchyme and epithelium has been known as a driver of tumor progression. We have considered such an interaction exists in liver cancer. The hepatic stellate cell, first described by Kupffer in the 19th centry, has emerged in the past 25 years as a remarkably versatile mesenchymal cell that is vital to hepatocellular function and the liver’s response to injury. Countless studies have explored the importance of hepatic stellate cells in liver fibrosis and repair, but its role in fibrogenesis and progression of liver tumor has been lacking for at least a decade. The current study indicates stromal myofibroblasts may promote the progression of intrahepatic cholangiocarcinoma and they could be derived from hepatic setllate cells by immunohistochemical study. Furthermore, there were no reports that researched the interaction between hepatic stellate cells and cholangiocarcinoma cells in vitro, and this study showed that the invasiveness and growth of cholangiocarcinoma cells were induced by hepatic stellate cells, using co-culture model. The remaining problem in this study is what promotes that interaction. Several cytokines has been reported to facilitate the interaction of pancreatic stellate cells and pancreatic adenocarcinoma. We need a better understanding of the factors related to the cross-talk of hepatic stellate cells and cholangiocarcinoma cells. Such understanding will promote and refine therapeutic approaches targeting hepatic stellate cells. |
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