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 language | English (US) |
|---|---|
| Pages (from-to) | 1-12 |
| Number of pages | 12 |
| Journal | Head and Neck Pathology |
| Volume | 2 |
| Issue number | 1 |
| DOIs | |
| State | Published - 2008 |
| Externally published | Yes |
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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
- Oncology
- Otorhinolaryngology
Cite this
Lipopolysaccharide-squamous cell carcinoma-monocyte interactions induce cancer-supporting factors leading to rapid STAT3 activation. / Kurago, Zoya B.; Lam-ubol, Aroonwan; Stetsenko, Anton; De La Mater, Chris; Chen, Yiyi; Dawson, Deborah V.
In: Head and Neck Pathology, Vol. 2, No. 1, 2008, p. 1-12.Research output: Contribution to journal › Article
}
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.
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
UR - http://www.scopus.com/inward/record.url?scp=77955236679&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77955236679&partnerID=8YFLogxK
U2 - 10.1007/s12105-007-0038-x
DO - 10.1007/s12105-007-0038-x
M3 - Article
C2 - 19603082
AN - SCOPUS:77955236679
VL - 2
SP - 1
EP - 12
JO - Head and Neck Pathology
JF - Head and Neck Pathology
SN - 1936-055X
IS - 1
ER -