Abstract
Bacteria and chronic inflammation are present in squamous cell carcinoma of the head and neck (HNSCC), but their roles in the pathogenesis of HNSCC are unclear. Our studies described here revealed that human monocytes co-cultured short term with HNSCC cells were more likely to express CD16, and CD16+ small mononuclear cells were common in HNSCC specimens. In addition, we identified monocytes as the primary source of LPS-induced IL-6 and TNF-alpha in the monocyte-HNSCC co-cultures. Remarkably, relative to LPS-stimulated monocytes cultured alone, HNSCC cells profoundly suppressed LPS-induced TNF-alpha in monocytes, without compromising IL-6 production. High levels of cytoprotective factors like IL-6 and low levels of TNF-alpha are important for the tumor microenvironment that enables tumor cell survival, affects monocyte differentiation and may contribute to tumor colonization by bacteria. This study provides novel observations that HNSCC cells affect monocyte phenotype and function, which are relevant to the regulation of the HNSCC microenvironment.
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Abbreviations
- CCR:
-
CC chemokine receptor
- DC:
-
Dendritic cell(s)
- DC-SIGN:
-
DC-specific intercellular adhesion molecule 3-grabbing non-integrin
- DMEM:
-
Dulbecco’s Modified Eagle’s Medium
- ELISA:
-
Enzyme-linked immunosorbent assay
- FACS:
-
Fluorescence-activated cell sorting
- FBS:
-
Fetal bovine serum
- GLM:
-
Generalized linear model
- HBD:
-
Human beta-defensin
- HLA-DR:
-
Human leukocyte antigen-DR (class II)
- HNSCC:
-
Head and neck squamous cell carcinoma
- HRP-DAB:
-
Horseradish peroxidase-diaminobenzidine
- IHC:
-
Immunohistochemistry
- IL:
-
Interleukin
- KSFM:
-
Keratinocyte Serum-Free Medium
- LPS:
-
Lipopolysaccharide
- MFI:
-
Mean fluorescence intensity
- PBS:
-
Phosphate-buffered saline
- SAS:
-
Statistical analysis software
- STAT:
-
Signal transducer and activator of transcription
- TCA:
-
Trichloroacetic acid
- TGF:
-
Transforming growth factor
- TLR:
-
Toll-like receptor
- TMB:
-
Tetramethylbenzidine
- TNF:
-
Tumor necrosis factor
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Acknowledgements
We thank the Department of Pathology, UI College of Medicine, and especially Teresa Duling, for access to flow cytometry. We thank Dr. Al Klingelhutz (University of Iowa) and Dr. David Levy (NYU) for the review and critique of the manuscript.
Supported by NIH2RO1DE11139-05A2 (ZBK), American Cancer Society Grant #IN-122V administered by The University of Iowa Holden Comprehensive Cancer Center (ZBK), Anandamahidol Foundation (AL), the University of Iowa Dental Student Research Assistantship program (DH), the Department of Oral Pathology, Radiology and Medicine, College of Dentistry, University of Iowa, and New York University College of Dentistry.
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Lam-ubol, A., Hopkin, D., Letuchy, E.M. et al. Squamous Carcinoma Cells Influence Monocyte Phenotype and Suppress Lipopolysaccharide-Induced TNF-alpha in Monocytes. Inflammation 33, 207–223 (2010). https://doi.org/10.1007/s10753-009-9175-6
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DOI: https://doi.org/10.1007/s10753-009-9175-6