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

Zoya Bronislavovna Kurago, Aroonwan Lam-ubol, Anton Stetsenko, Chris De La Mater, Yiyi Chen, Deborah V. Dawson

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1-12
Number of pages12
JournalHead and Neck Pathology
Volume2
Issue number1
DOIs
StatePublished - Dec 1 2008
Externally publishedYes

Fingerprint

Lipopolysaccharides
Monocytes
Squamous Cell Carcinoma
Neoplasms
Interleukin-6
Vascular Endothelial Growth Factor A
Cell Line
Stomatitis
Chemotactic Factors
Carcinoma in Situ
Coculture Techniques
Chemokines
Dendritic Cells
Phosphorylation
Cytokines

Keywords

  • Cytokines
  • Inflammation
  • Interleukin-6
  • Lipopolysaccharide
  • Monocytes/macrophages
  • Oral squamous cell carcinoma
  • STAT3
  • Toll-like receptor
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Otorhinolaryngology
  • Oncology

Cite this

Lipopolysaccharide-squamous cell carcinoma-monocyte interactions induce cancer-supporting factors leading to rapid STAT3 activation. / Kurago, Zoya Bronislavovna; Lam-ubol, Aroonwan; Stetsenko, Anton; De La Mater, Chris; Chen, Yiyi; Dawson, Deborah V.

In: Head and Neck Pathology, Vol. 2, No. 1, 01.12.2008, p. 1-12.

Research output: Contribution to journalArticle

Kurago, Zoya Bronislavovna ; Lam-ubol, Aroonwan ; Stetsenko, Anton ; De La Mater, Chris ; Chen, Yiyi ; Dawson, Deborah V. / Lipopolysaccharide-squamous cell carcinoma-monocyte interactions induce cancer-supporting factors leading to rapid STAT3 activation. In: Head and Neck Pathology. 2008 ; Vol. 2, No. 1. pp. 1-12.
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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.

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