The white blood cells known as macrophages are an essential part of our immune system. However, a specific type of macrophages is also found in tumours, where they play an important role in the formation of blood vessels.
The team of Professor Massimiliano Mazzone (KU Leuven/VIB) and Dr Mathias Wenes (KU Leuven/VIB) examined the impact of changing the metabolism of the macrophages. By blocking a specific gene in the macrophages, they stimulated the process that cells use to convert sugar into energy.
“Too much sugar overstimulates the cells that form the blood vessels of the tumour,” explains Professor Mazzone. “As a result, these cells start creating a blood vessel network that is chaotic and irregular. This structure is typical of cancer and makes it easier for the cancer cells to enter the bloodstream and invade other organs.”
“By changing the metabolism of the macrophages, we were able to make them ‘steal’ sugar from the blood vessel cells. As a result, the blood vessel cells create a different type of vessel network. Due to its structure, this network forms a strong vessel barrier around the tumour and thus prevents cancer cells from escaping.”
Professor Mazzone joined forces with the lab of Professor Peter Carmeliet (VIB / KU Leuven), specialized in blood vessel formation, and with metabolism expert Bart Ghesquière (VIB / KU Leuven). The researchers investigated the effect of so-called mTOR inhibitors aimed at reducing tumour growth.
“These inhibitors are only partially effective in patients,” Mazzone explains. “We found that they can actually increase the spread of cancer in mice because they hinder the conversion of sugar into energy in macrophages. We’re currently examining whether we could use our findings to predict people’s resistance to mTOR inhibitors.”