Neutrophils promote liver metastasis via Mac-1 mediated interactions with circulating tumor cells
Menée à l'aide d'un modèle murin, cette étude met en évidence un mécanisme par lequel, en interagissant avec les cellules tumorales circulantes, les neutrophiles favorisent la formation de métastases hépatiques
Although circulating neutrophils are associated with distant metastasis and poor outcome in a number of epithelial malignancies, whether neutrophils play an active causal role in the metastatic cascade remains unclear. Using in vivo models of metastasis, we found that neutrophils promote cancer cell adhesion within liver sinusoids and thereby influence metastasis. Neutrophil depletion prior to cancer cell inoculation resulted in a decreased number of gross metastases in an intra-splenic model of liver metastasis. This effect was reversed when inflamed neutrophils were co-inoculated with cancer cells. In addition, early adhesion within liver sinusoids was inhibited in the absence of neutrophils and partially restored with a short perfusion of isolated activated neutrophils. Intra-vital microscopy showed that cancer cells adhered directly on top of arrested neutrophils, suggesting that neutrophils may act as a bridge to facilitate interactions between cancer cells and the liver parenchyma. The adhesion of lipopolysaccharide-activated neutrophils to cancer cells was mediated by neutrophil Mac-1/ICAM-1. Our findings therefore demonstrate a novel role for neutrophils in the early adhesive steps of liver metastasis.
Cancer Research 2012