This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Stathopoulos, G. T. Articles by Fingleton, B. Search for Related Content PubMed PubMed Citation Articles by Stathopoulos, G. T. Articles by Fingleton, B.

---

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)