PMID- 21437888
OWN - NLM
STAT- MEDLINE
DCOM- 20111115
LR  - 20211020
IS  - 1097-0142 (Electronic)
IS  - 0008-543X (Print)
IS  - 0008-543X (Linking)
VI  - 117
IP  - 19
DP  - 2011 Oct 1
TI  - Neutrophil interactions with sialyl Lewis X on human nonsmall cell lung carcinoma 
      cells regulate invasive behavior.
PG  - 4493-505
LID - 10.1002/cncr.26059 [doi]
AB  - 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 
      alpha(1,3/1,4) fucosyltransferase (FucT-III). Tumor necrosis factor-alpha (TNF-alpha) 
      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-alpha 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-alpha up-regulated sLeX expression and increased E-selectin binding. 
      Transfected cells secreted high levels of interleukin 8, growth-regulated 
      oncogene-alpha, and mast cell proteinase-1. Cells exposed to rhTNF-alpha, 
      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.
CI  - Copyright (c) 2011 American Cancer Society.
FAU - St Hill, Catherine A
AU  - St Hill CA
AD  - Department of Veterinary Clinical Sciences, University of Minnesota, Veterinary 
      Medical Center, St. Paul, Minnesota, USA. sthil001@umn.edu
FAU - Krieser, Katherine
AU  - Krieser K
FAU - Farooqui, Mariya
AU  - Farooqui M
LA  - eng
GR  - K08 CA111829/CA/NCI NIH HHS/United States
GR  - K08 CA111829-04/CA/NCI NIH HHS/United States
GR  - 5K08CA111829-04/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20110322
PL  - United States
TA  - Cancer
JT  - Cancer
JID - 0374236
RN  - 0 (E-Selectin)
RN  - 0 (Oligosaccharides)
RN  - 0 (RNA, Messenger)
RN  - 0 (Sialyl Lewis X Antigen)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.4.1.- (Fucosyltransferases)
RN  - EC 2.4.1.65 (3-galactosyl-N-acetylglucosaminide 4-alpha-L-fucosyltransferase)
SB  - IM
MH  - Blotting, Western
MH  - Carcinoma, Non-Small-Cell Lung/*immunology/metabolism/*pathology
MH  - E-Selectin/genetics/metabolism
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Flow Cytometry
MH  - Fucosyltransferases/genetics/metabolism
MH  - Humans
MH  - Immunoenzyme Techniques
MH  - Lung Neoplasms/*immunology/metabolism/*pathology
MH  - Neoplasm Invasiveness
MH  - Neutrophils/*immunology/metabolism
MH  - Oligosaccharides/genetics/*metabolism
MH  - RNA, Messenger/genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sialyl Lewis X Antigen
MH  - Tumor Cells, Cultured
MH  - Tumor Necrosis Factor-alpha/genetics/metabolism
PMC - PMC3134589
MID - NIHMS274316
EDAT- 2011/03/26 06:00
MHDA- 2011/11/16 06:00
PMCR- 2012/10/01
CRDT- 2011/03/26 06:00
PHST- 2010/01/18 00:00 [revised]
PHST- 2010/11/23 00:00 [received]
PHST- 2011/02/02 00:00 [accepted]
PHST- 2011/03/26 06:00 [entrez]
PHST- 2011/03/26 06:00 [pubmed]
PHST- 2011/11/16 06:00 [medline]
PHST- 2012/10/01 00:00 [pmc-release]
AID - 10.1002/cncr.26059 [doi]
PST - ppublish
SO  - Cancer. 2011 Oct 1;117(19):4493-505. doi: 10.1002/cncr.26059. Epub 2011 Mar 22.