Lipopolysaccharide-squamous cell carcinoma-monocyte interactions induce cancer-supporting factors leading to rapid STAT3 activation

被引：36
作者：
Kurago Z.B. [1 ]
Lam-ubol A. [2 ]
Stetsenko A. [2 ]
De La Mater C. [2 ]
Chen Y. [3 ]
Dawson D.V. [3 ,4 ]
机构：
[1] Department of Oral and Maxillofacial Pathology, Radiology and Medicine, College of Dentistry, New York University, New York
[2] Department of Oral Pathology, Radiology and Medicine, College of Dentistry, University of Iowa, Iowa City
[3] Department of Biostatistics, College of Public Health, University of Iowa, Iowa City
[4] Department of Preventive and Community Dentistry, College of Dentistry, University of Iowa, Iowa City
来源：
Head and Neck Pathology | 2008年 / 2卷 / 1期
基金：
美国国家卫生研究院;
关键词：
Cytokines; Inflammation; Interleukin-6; Lipopolysaccharide; Monocytes/macrophages; Oral squamous cell carcinoma; STAT3; Toll-like receptor; Vascular endothelial growth factor;
D O I：
10.1007/s12105-007-0038-x
中图分类号：
学科分类号：
摘要：
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. © Humana 2008.
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页码：1 / 12
页数：11
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