TY - JOUR
T1 - Lipopolysaccharide-squamous cell carcinoma-monocyte interactions induce cancer-supporting factors leading to rapid STAT3 activation
AU - Kurago, Zoya B.
AU - Lam-ubol, Aroonwan
AU - Stetsenko, Anton
AU - De La Mater, Chris
AU - Chen, Yiyi
AU - Dawson, Deborah V.
N1 - Funding Information:
Acknowledgements We thank Dr. G. B. Schneider, Rebecca Zacharias and Denise Seabold (College of Dentistry, University of Iowa) for the generous help with Western blotting; Ms. Crystal Fairlie (College of Dentistry, University of Iowa) for assistance with cutting tissue sections, and Dr. O. Rokhlin (Department of Pathology, University of Iowa), Dr. J. McCutcheon (New York University), and Dr. C. T. Lutz (University of Kentucky) for the review and critique of the manuscript. Supported by NIDCR Dental Student Research Fellowship (C. De La Mater), Anandamahidol Foundation (A. Lam-ubol), American Cancer Society Grant #IN-122V administered by The University of Iowa Holden Comprehensive Cancer Center, NIH R01 DE11139, University of Iowa College of Dentistry Seed Grant and the Department of Oral Pathology, Radiology and Medicine at the College of Dentistry, University of Iowa.
PY - 2008
Y1 - 2008
N2 - Oral and oro-pharyngeal squamous cell carcinomas (OSCC) exhibit surface breach, and recent studies have demonstrated bacterial contamination of primary and metastatic OSCC. Increasing concentrations of inflammatory products, such as interleukin (IL)-6 and vascular endothelial growth factor (VEGF), correlate with, and contribute to, cancer progression, but their regulation in OSCC is poorly understood. We hypothesized that monocyte- lineage cells and bacterial contamination may contribute important inflammatory products that can support OSCC progression. We found that relative to nonspecific chronic mucositis, oral carcinoma-in-situ/superficially- invasive OSCC contained more monocyte-lineage cells. In vitro, we used lipopolysaccharide (LPS) to model bacterial contamination, and evaluated the effects of oral and oropharyngeal (O)SCC-monocyte interactions and of LPS on OSCC cells and on the production of IL-6 and VEGF. OSCC cell lines varied in constitutive cytokine and chemokine production, and OSCC-monocyte interactions in the absence of LPS stimulated IL-6 and VEGF occasionally, while LPS-OSCC-monocyte interactions were always strongly stimulatory. Importantly, LPS independently stimulated some OSCC lines to secrete monocyte-dendritic cell chemoattractants CCL2 and/or CCL20, as well as IL-6 and/or VEGF. While very little constitutive Y705-STAT3 phosphorylation (pY705-STAT3) was detectable in HNSCC lines, IL-6 rapidly induced pY705-STAT3 in OSCC lines that produced little IL-6 constitutively. Supernatants from LPS-OSCC-monocyte co-cultures always rapidly and strongly activated STAT3, which was partly due to IL-6. We conclude that monocytes and microbial contamination have the potential to contribute to OSCC progression, as STAT3 activation in OSCC cells depends on soluble factors, which are consistently available through LPS-OSCC-monocyte interactions.
AB - Oral and oro-pharyngeal squamous cell carcinomas (OSCC) exhibit surface breach, and recent studies have demonstrated bacterial contamination of primary and metastatic OSCC. Increasing concentrations of inflammatory products, such as interleukin (IL)-6 and vascular endothelial growth factor (VEGF), correlate with, and contribute to, cancer progression, but their regulation in OSCC is poorly understood. We hypothesized that monocyte- lineage cells and bacterial contamination may contribute important inflammatory products that can support OSCC progression. We found that relative to nonspecific chronic mucositis, oral carcinoma-in-situ/superficially- invasive OSCC contained more monocyte-lineage cells. In vitro, we used lipopolysaccharide (LPS) to model bacterial contamination, and evaluated the effects of oral and oropharyngeal (O)SCC-monocyte interactions and of LPS on OSCC cells and on the production of IL-6 and VEGF. OSCC cell lines varied in constitutive cytokine and chemokine production, and OSCC-monocyte interactions in the absence of LPS stimulated IL-6 and VEGF occasionally, while LPS-OSCC-monocyte interactions were always strongly stimulatory. Importantly, LPS independently stimulated some OSCC lines to secrete monocyte-dendritic cell chemoattractants CCL2 and/or CCL20, as well as IL-6 and/or VEGF. While very little constitutive Y705-STAT3 phosphorylation (pY705-STAT3) was detectable in HNSCC lines, IL-6 rapidly induced pY705-STAT3 in OSCC lines that produced little IL-6 constitutively. Supernatants from LPS-OSCC-monocyte co-cultures always rapidly and strongly activated STAT3, which was partly due to IL-6. We conclude that monocytes and microbial contamination have the potential to contribute to OSCC progression, as STAT3 activation in OSCC cells depends on soluble factors, which are consistently available through LPS-OSCC-monocyte interactions.
KW - Cytokines
KW - Inflammation
KW - Interleukin-6
KW - Lipopolysaccharide
KW - Monocytes/macrophages
KW - Oral squamous cell carcinoma
KW - STAT3
KW - Toll-like receptor
KW - Vascular endothelial growth factor
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U2 - 10.1007/s12105-007-0038-x
DO - 10.1007/s12105-007-0038-x
M3 - Article
C2 - 19603082
AN - SCOPUS:77955236679
SN - 1936-055X
VL - 2
SP - 1
EP - 12
JO - Head and Neck Pathology
JF - Head and Neck Pathology
IS - 1
ER -