Host nuclear factor-kappaB activation potentiates lung cancer metastasis.
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-kappaB (NF-kappaB), 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-kappaB-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-kappaB 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-kappaB activity in host tissue is a significant factor in the development of lung metastasis.
Stathopoulos
Georgios T
GT
Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-6840, USA.
Sherrill
Taylor P
TP
Han
Wei
W
Sadikot
Ruxana T
RT
Yull
Fiona E
FE
Blackwell
Timothy S
TS
Fingleton
Barbara
B
D000260:Adenoviruses, Human / Q000235:genetics; D000818:Animals; D002455:Cell Division; D045744:Cell Line, Tumor; D018932:Chemokine CCL2 / Q000032:analysis; D054412:Chemokine CCL8 / Q000032:analysis; D017930:Genes, Reporter; D005822:Genetic Vectors; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D016328:NF-kappa B / Q000502:physiology*; D009362:Neoplasm Metastasis / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
C111835:CCL2 protein, human; C515453:CCL8 protein, human; D018932:Chemokine CCL2; D054412:Chemokine CCL8; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D020780:Matrix Metalloproteinase 9