Expression of stem cell factor and its receptor c-Kit during the development of intrahepatic cholangiocarcinoma
| Autor: | T. Mansuroglu, László Füzesi, Pierluigi Ramadori, Kristoff Hammerich, Giuliano Ramadori, Jozsef Dudas, Ihtzaz Ahmed Malik |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Male
Pathology medicine.medical_specialty Cirrhosis Blotting Western Cell Stem cell factor Thioacetamide Biology Pathology and Forensic Medicine Cholangiocarcinoma Rats Sprague-Dawley 03 medical and health sciences Liver Neoplasms Experimental 0302 clinical medicine medicine Animals RNA Messenger Receptor Molecular Biology 030304 developmental biology Stem Cell Factor 0303 health sciences Liver cell Kupffer cell Cell Biology medicine.disease Immunohistochemistry Molecular biology Liver regeneration Rats 3. Good health Proto-Oncogene Proteins c-kit Bile Ducts Intrahepatic medicine.anatomical_structure Liver 030220 oncology & carcinogenesis embryonic structures Hepatocytes Signal transduction |
| Zdroj: | Laboratory Investigation. 89:562-574 |
| ISSN: | 0023-6837 |
| DOI: | 10.1038/labinvest.2009.15 |
| Popis: | Stem cell factor (SCF) and its receptor, c-Kit, constitute an important signal transduction system with proliferative and anti-apoptotic functions. Besides regulating hemopoietic stem cell proliferation and liver regeneration, it has been implicated in the regulation of human malignancies. However, the cellular expression of the SCF-c-Kit gene system in the liver during cholangiocarcinogenesis has not been studied to date. The protein- and mRNA-expression levels of SCF and c-Kit genes were examined in normal rat liver, in isolated normal rat liver cells and in a thioacetamide-induced rat model of intrahepatic cholangiocarcinoma (CC). Immunohistochemical analysis of the normal liver showed that SCF is expressed in the wall of the hepatic artery and in some cells, which were located along the sinusoids, although it was absent from hepatocytes and biliary epithelial cells. The mRNA analysis of isolated normal liver cell populations revealed a co-expression of SCF- and c-Kit-mRNA in sinusoidal endothelial cells and in Kupffer cells, whereas passaged and cultured liver myofibroblasts (MFs) expressed only SCF. Low levels of the SCF- and c-Kit-mRNA expression could be detected in isolated hepatocytes of the normal liver. Immunohistochemical analysis of the CC tissue showed SCF positivity in proliferating biliary cells (CK-19(+)), in macrophages (ED-1(+)) and in MFs (alpha-smooth-muscle-actin, alpha-SMA(+)) of the tumoral microenvironment. c-Kit-positivity could be detected on hepatocytes of the regenerating nodules and on the proliferating bile ducts of CC. Compared with the normal liver tissue, SCF-mRNA from the CC tissue was upregulated up to 20-fold, whereas c-Kit-mRNA was upregulated up to fivefold. These data indicate that several cell populations may become able to express SCF and/or c-Kit during cholangiocarcinogenesis. Therefore, the SCF-c-Kit system may contribute to tumor development, for instance, by inducing proliferation of hepatocytes and of biliary cells and by acting as a surviving factor for CC cells. |
| Databáze: | OpenAIRE |
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