Neutrophil interactions with sialyl Lewis X on human nonsmall cell lung carcinoma cells regulate invasive behavior.

Abstract

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.

• Authors: Catherine A St Hill, Katherine Krieser, Mariya Farooqui
• Journal: Cancer (Cancer) Vol. 117 Issue 19 Pg. 4493-505 (Oct 01 2011) ISSN: 1097-0142 [Electronic] United States
• PMID: 21437888 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2011 American Cancer Society.

Chemical References

• E-Selectin
• Oligosaccharides
• RNA, Messenger
• Sialyl Lewis X Antigen
• Tumor Necrosis Factor-alpha
• Fucosyltransferases
• 3-galactosyl-N-acetylglucosaminide 4-alpha-L-fucosyltransferase

Topics

• Blotting, Western
• Carcinoma, Non-Small-Cell Lung (immunology, metabolism, pathology)
• E-Selectin (genetics, metabolism)
• Enzyme-Linked Immunosorbent Assay
• Flow Cytometry
• Fucosyltransferases (genetics, metabolism)
• Humans
• Immunoenzyme Techniques
• Lung Neoplasms (immunology, metabolism, pathology)
• Neoplasm Invasiveness
• Neutrophils (immunology, metabolism)
• Oligosaccharides (genetics, metabolism)
• RNA, Messenger (genetics)
• Reverse Transcriptase Polymerase Chain Reaction
• Sialyl Lewis X Antigen
• Tumor Cells, Cultured
• Tumor Necrosis Factor-alpha (genetics, metabolism)