Hepatocellular carcinoma (GC) is the most common form of liver cancer and the third leading cause of death from cancer worldwide. Although patients with GC took advantage of recent improvements in the diagnosis and various treatment methods, their average life expectancy is still only 16.2 months, while patients with lung metastases of life for less than 6 months.
Lung metastases occur when tumor cells of the liver into the bloodstream. This process involves a series of interactions of the tumor cells and the host, but the precise details are not known. Currently, the Japanese team of researchers led by the University of Kanazawa, conducted a detailed study of the role of two types of white white blood cells (macrophages) light and a variety of molecules associated with inflammation in a mouse model of metastasis. The study was published in the Journal of Immunology.
animal model was prepared by injecting murine cell line HA in mice strands, which led to an increase in small metastasis in the lungs. By controlling the metastasis, the team discovered the accumulation of two types of macrophages in the lung: interstitial macrophages (IM) and alveolar macrophages (AMs).
«IM obtained from the circulation, and is already known to help the survival and growth of lung tumors", - says first author Takuto Nosaka. "Conversely, AMs occur from the tissue lining the inside air sacs (alveoli) in the lungs, and has only recently been shown to be involved in metastasis. Their function in lung metastasis was unclear, but the increase observed in this model is the first proof that they have to play an important role. "
Indeed, AMs around murine lung nodules produce more inflammatory leukotriene B4 (LTB4) lipids than IM. LTB4 activates immune cells and directly increases the proliferation and invasion of human and mouse cancer cells, including cells of the Civil Code. It was shown that AM promote the growth of tumor cells in the lung metastatic nodes through secretion of LTB4.
"Then, we focused on recruiting AM from the bloodstream to the lungs, and showed that it is controlled by the IM, which express the signaling molecule CCL2», - says corresponding author Naofumi Mukayda. «CCL2-CCR2 receptor is expressed AM, and binding of the two molecules controls accumulation AM».
This interaction AM-IM contributes to the progression of lung metastasis by the production of LTB4, which suggests the possibility of developing a new approach to treatment which targets these molecules.