AsianScientist (Oct. 8, 2014) – A University of Tokyo research group has discovered that AIM (apoptosis inhibitor of macrophage), a protein that plays a preventive role in obesity progression, can also prevent tumor development in mice liver cells. This discovery, published in Cell Reports, could lead to a therapy for hepatocellular carcinoma (HCC), the most common type of liver cancer and the third most common cause of cancer deaths.
Professor Toru Miyazaki’s group at the Laboratory of Molecular Biomedicine from Pathogenesis, in the Faculty of Medicine has shown that AIM (also known as CD5L) accumulates on the cell membrane of HCC cells, where it triggers the complement cascade, a highly efficient process of eliminating cancer cells.
Experiments showed that mice unable to produce AIM fed on a high-fat diet for a year developed multiple liver tumors. Additionally, when the same type of mice were fed the high-fed diet for 45 weeks but treated with AIM, they showed no signs of cancer, indicating that cancerous cells were being destroyed.
The group had previously found AIM, identifying its supportive role for the immune system and protective role in obesity progression of fat cells. Now they have found that AIM is also involved in eliminating cancer cells. The group revealed that AIM accumulates on the surface of mice HCC cells, but not on normal cells and showed that AIM interferes with proteins that normally suppress the complement cascade, triggering a process that leads to necrosis and elimination of the cancerous cells.
“Because of its resistance to chemotherapy, HCC is now the third most common cause of cancer-related deaths, and therefore, it is certainly desirable to identify the preventive machinery against HCC,” says Prof. Miyazaki.
“The most exciting finding for us is that AIM behaves in two different ways in preventing liver diseases. It enters into normal hepatocytes to keep them skinny, which prevents the buildup of fat inside cells seen in steatosis, whereas it accumulates on the surface of HCC cells to kill them.”
Given that AIM also gathers on the surface of human HCC, it may be possible to develop AIM as a therapy for human HCC.
Professor Miyazaki continues, “It is surprising that we do have an excellent system to eliminate undesired cancer cells, and that this system may certainly be therapeutically applicable not only to HCC, but also more broadly to other types of cancer.”
The article can be found at: Maehara et al. (2014) Circulating AIM Prevents Hepatocellular Carcinoma through Complement Activation.
——
Source: University of Tokyo.
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.
