Role of pulmonary macrophages in initiation of lung metastasis in anaplastic thyroid cancer

Several clinical studies have demonstrated that increased macrophage infiltration into tumors confers metastatic potential and poor prognosis in cancer. Preclinical studies are needed to develop new strategies for countering metastasis. Our study was designed to investigate the impact of pulmonary macrophages on lung metastasis of anaplastic thyroid cancer (ATC). ATC (CAL-62) and macrophage (Raw264.7) were transfected with the effluc (CAL-62/effluc, Raw264.7/effluc). Coculture and migration assays were used to assess the effect of Raw264.7 or THP1 (human macrophage) (or conditioned medium) on the proliferation and/or migration of CAL-62/effluc cells in vitro. The effect of clodro-lipo or PBS-lipo on macrophage depletion was confirmed in vitro and in vivo. CAL-62/effluc cells (1 x 10(6)) were intravenously injected into nude mice 24 h after clodro-lipo or PBS-lipo administration. Effect of clodro-lipo on the lung metastasis of CAL-62/effluc was assessed by bioluminescence imaging (BLI). Micro computed tomography (micro-CT) and histology. BLI signals of CAL-62/effluc and Raw264.7/effluc increased to cell number. Raw264.7 cells and THP1 cells promoted CAL-62/effluc proliferation, and conditioned medium of Raw264.7 cells promoted CAL-62/effluc migration. Clodro-lipo significantly depleted pulmonary macrophages in vitro and in vivo. Intensity of BLI signals in ATC lung metastasis was weaker in the clodro-lipo group than PBS-lipo control. Micro-CT imaging and hematoxylin/eosin staining revealed smaller tumor masses in the clodro-lipo group than PBS-lipo control. Our findings indicate that pulmonary macrophages have an important role in initiation of lung metastasis of ATC. New therapeutic strategies that preclude initiation of pulmonary metastasis could potentially be developed by targeting pulmonary macrophages. What's new? Survival for anaplastic thyroid cancer (ATC) patients is more often measured in months than years. One reason is the disease quickly metastasizes, often spreading to the lungs. These authors set out to study how macrophages enable the cancer to spread. Macrophages play a key role in inflammation, and inflammation sets the stage for tumors to take root. In this study, the authors tested clodronate, which gets rid of macrophages, in both ATC tumor cells and in mice. The clodronate did deplete the macrophages, and successfully thwarted the growth of tumors in the lungs.