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Angiogenesis, Metastasis, and the Cellular Microenvironment

Host Nuclear Factor-B Activation Potentiates Lung Cancer Metastasis

¹ Division of Allergy, Pulmonary and Critical Care Medicine; ² Department of Cancer Biology, Vanderbilt University School of Medicine; and ³ Department of Veterans Affairs, VA Tennessee Valley Healthcare System, Nashville, Tennessee

Requests for reprints: Barbara Fingleton, Department of Cancer Biology, Vanderbilt University School of Medicine, 734 PRB, 2220 Pierce Avenue, Nashville, TN 37232-6840. Phone: 615-936-5877; Fax: 615-936-2911. E-mail: Barbara.fingleton{at}vanderbilt.edu

Epidemiologic and experimental evidence suggests that a link exists between inflammation and cancer, although this relationship has only recently begun to be elucidated for lung cancer, the most frequently fatal human tumor. Nuclear factor-B (NF-B), a transcription factor that controls innate immune responses in the lungs, has been implicated as an important determinant of cancer cell proliferative and metastatic potential; however, its role in lung tumorigenesis is uncertain. Here, we specifically examine the role of NF-B–induced airway inflammation in lung cancer metastasis using a model of intravenous injection of Lewis lung carcinoma cells into immunocompetent C57Bl/6 mice. Induction of lung inflammation by direct and specific NF-B activation in airway epithelial cells potentiates lung adenocarcinoma metastasis. Moreover, we identify resident lung macrophages as crucial effectors of lung susceptibility to metastatic cancer growth. We conclude that NF-B activity in host tissue is a significant factor in the development of lung metastasis. (Mol Cancer Res 2008;6(3):364–71)