This can happen through an interaction between two types of cells called 'alveolar macrophages' (AMs) and 'interstitial macrophages' (IMs).
A Japanese team of researchers led by Kanazawa University has undertaken a detailed investigation of the role of two different scavenger white blood cells (macrophages) of the lung, and a myriad of molecules associated with inflammation in a mouse model of metastasis.
‘Cells that clean the lung called ‘dust cells’ or ‘alveolar macrophages’ (AMs) may cause the spread of liver cancer to the lung.’
The animal model was produced by injecting a mouse HCC cell line into the veins of mice, which resulted in the growth of small metastatic lung nodules that resembled HCC lung metastasis in humans. By monitoring the metastasis, the team detected an accumulation of two types of macrophages in the lungs: interstitial macrophages (IMs) and alveolar macrophages (AMs).
"IMs derive from the circulation, and were already known to aid the survival and growth of lung tumors," study first author Takuto Nosaka says. "Conversely, AMs come from tissue lining the inside of air sacs (alveoli) in the lungs, and were only recently shown to be involved in metastasis. Their function in lung metastasis was unclear, but their observed increase in this model is the first evidence that they must play an important role."
Indeed, AMs around the mouse lung nodules produced more of the inflammatory lipid leukotriene B4 (LTB4) than IMs. LTB4 activates immune cells, and directly boosts the proliferation and invasiveness of both human and mouse cancer cells, including HCC cells. AMs were also shown to directly promote tumor cell growth at metastatic lung nodules through LTB4 secretion.
"We next focused on AM recruitment from the bloodstream into the lungs, and showed that this was controlled by IMs which express the signaling molecule CCL2," corresponding author Naofumi Mukaida explains. "The CCL2 receptor, CCR2, is expressed by AMs, and binding of the two molecules controls AM accumulation."
This AM-IM interaction contributes to the progression of lung metastasis through the production of LTB4, suggesting the potential for developing a novel treatment approach that targets these molecules
Hepatocellular carcinoma (HCC) is the most common form of liver cancer
and the third biggest cause of death from cancer worldwide.
The study is published in the Journal of Immunology