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Carcinogenic role of a protein in liver decoded
01 September 2014
Medical University of Vienna
The human protein EGFR controls cell growth. It has mutated in case of many cancer cells or exists in excessive numbers. For this reason it serves as a point of attack for target-oriented therapies. A study group at the Comprehensive Cancer Centre of Medical University of Vienna and AKH Vienna under the guidance of Maria Sibilia from the Institute for Cancer Research has now discovered that the risk of this protein does not - as previously assumed - depend on its presence within the tumour cell, but rather from its activity in the cells adjacent to the tumour. EGFR can play a major role in stimulating the tumour in the macrophages (immune cells) of the liver during the formation of the dangerous liver carcinoma.
The EGF Receptor (Epidermal Growth Factor Receptor, EGFR) is a protein which, as a transmembrane receptor, controls a multitude of vital processes in the cell. In human beings, the EGF Receptor is present in many cells types and plays an important role in many types of cancer. It is present in various kinds of tumours in excessive amounts and/or in mutated form, which causes the tumour cells to grow and multiply. For this reason the EGFR serves as a point of attack in many treatment strategies. In the process, its function is inhibited with the objective of slowing down the growth of the tumour cell.
The liver cell carcinoma (hepatocellular carcinoma, short HCC) is one of the most frequent malignant tumours worldwide. Approximately six percent of all cancers in men and about three percent in women are liver cell carcinomas. It is the second most frequent cause of death associated with cancer. Risk factors for HCC include liver diseases through Hepatitis B and C infections as well as alcohol abuse or the classic "fatty liver".
Up to now, the tumour-promoting role of EGFR has only been linked with its expression directly in the tumour cells. However, the study group of Maria Sibilia, Manager of the Institute for Cancer Research at the Medical University of Vienna and Deputy Manager of the Comprehensive Cancer Centre, in cooperation with the research groups of Michael Trauner and Markus Peck-Radosavljevic at the clinical division for gastroenterology and hepatology (Manager: Michael Trauner) as well as the Eastern Hepatobiliary Surgery Institute/Hospital in Shanghai discovered that EGFR plays a more decisive role in the macrophages of the liver (these are important cells of the immune system which are called Kupffer cells in the liver) with respect to the growth of the liver cell carcinoma than previously assumed.
"In this study we were able to prove that the inhibition of EGFR has a tumour inhibiting effect on the macrophages and not its inhibition on the tumour cell itself", explains Maria Sibilia. However, if the EGFR conversely exists on these macrophages in an excessive number, it can promote the growth of the tumour. Its existence on the macrophages reduces the chance of survival for HCC patients.
This could explain why EGFR inhibitors utilised for cancer treatment and aiming directly for the tumour cells have achieved clinically disappointing results in the fight against the liver cell carcinoma in the past. For the first time, this study proves the tumour-promoting mechanism for EGFR in non-tumour cells, which could lead to more effective and precise treatment strategies with macrophages as a point of approach in the future.