Pulmonary Inflammation Generates Chemotactic Activity for Tumor Cells and Promotes Lung Metastasis

Previous studies have demonstrated a chemotactic factor for tumor ceils in inflammatory peritoneal exudates. Because the lung is a frequent site of inflammation and of secondary tumors, we looked for tumor cell chemotactic factors in alveolar inflammatory exudates and examined the effect of inflammation on the localization and metastasis of circulating syngenic fibrosarcoma cells. Intratracheal injections of a 1-mg carbon suspension (0.03-μ particles in 0.1 ml sterile water) were given to C57 b1/6 mice that were killed between 6 h and 28 days later. The total number of cells recovered in bronchoalveolar lavage (BAL) fluids rose from 8 × 104 to 240 × 104, and was maximal at 3 days. Neutrophils accounted for more than 75% of the inflammatory cells in the first week when there was a greater than twentyfold rise in the levels of glucosaminidase in lavage fluids. Injection of water alone caused a mild inflammatory response that subsided rapidly. In Boyden chambers, the tumor cells demonstrated chemotactic responses to lavage supernatants from animals with inflamed lungs, and the magnitude of response correlated directly with the number of neutrophils (r = 0.60) or total exudate cells (r = 0.47) but not with macrophages (r = 0.05). Intravenous injection of 2 × 105 131I-iododeoxyuridine labeled tumor cells on the third to fifth day after intratracheal injection was followed after 24 h by pulmonary localization of 3 to 5 times more tumor cells in inflamed lungs than in control animals. Similarly, 7 to 21 days after injection of unlabeled tumor cells, there were 2 to 4.6 times more grossly detectable metastases in the lungs of animals with pulmonary inflammation (p < 0.025). We conclude that acute pulmonary inflammation can result in the generation of chemotactic activity for neoplastic cells and may promote tumor metastasis at that site.