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Neutrophil interactions with sialyl Lewis X on human nonsmall cell lung carcinoma cells regulate invasive behavior
Author(s) -
St. Hill Catherine A.,
Krieser Katherine,
Farooqui Mariya
Publication year - 2011
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.26059
Subject(s) - sialyl lewis x , transfection , lewis lung carcinoma , cancer research , matrigel , flow cytometry , tumor necrosis factor alpha , pathology , cytokine , proinflammatory cytokine , cell culture , medicine , metastasis , selectin , microbiology and biotechnology , biology , immunology , cancer , cell adhesion molecule , inflammation , angiogenesis , genetics
BACKGROUND: The carbohydrate sialyl Lewis X (sLeX) is expressed on leukocytes and carcinoma cells and binds to selectins during inflammatory processes and early metastasis. Synthesis of sLeX depends on activity of enzymes, including α(1,3/1,4) fucosyltransferase ( FucT‐III ). Tumor necrosis factor‐α (TNF‐α) up‐regulates FucT‐III , resulting in increased sLeX in the airways of patients with respiratory disease; however, the mechanisms that regulate sLeX in the inflammatory tumor microenvironment are not well understood. METHODS: The authors stably transfected human lung carcinoma cell lines with the FucT‐III gene and exposed them to TNF‐α to investigate its role in regulation of sLeX expression and selectin‐binding ability using semiquantitative real‐time polymerase chain reaction and flow cytometry. Cytokine expression was examined in transfected cells using chemiluminescent arrays and enzyme‐linked immunosorbent assays, and invasion was studied using Matrigel assays and alterations in morphology. Human lung tissue arrays were analyzed for immunohistochemical detection of sLeX and neutrophils. RESULTS: Stimulation of FucT‐III –transfected cells with recombinant human (rh) TNF‐α up‐regulated sLeX expression and increased E‐selectin binding. Transfected cells secreted high levels of interleukin 8, growth‐regulated oncogene‐α, and mast cell proteinase‐1. Cells exposed to rhTNF‐α, neutrophil‐conditioned media, and cultures with a 5:1 ratio of neutrophils to cancer cells had significantly increased sLeX expression and invasiveness and underwent nonadherent morphologic changes. In lung carcinomas, but not in normal lung tissues, 71% of tumors were highly positive for sLeX expression in areas of increased neutrophil infiltration. CONCLUSIONS: The current results indicated that neutrophils may be recruited to areas of FucT‐III activity and sLeX expression in lung carcinomas to enhance the invasive and metastatic potential of lung cancer cells. Cancer 2011. © 2011 American Cancer Society.