Human beta-defensin-3 (hBD-3) upregulated by LPS via epidermal growth factor receptor (EGFR) signaling pathways to enhance lymphatic invasion of oral squamous cell carcinoma.
OBJECTIVE
In this study, the hypothesis that hBD-3 is upregulated by LPS via epidermal growth factor receptor (EGFR) signaling pathways to enhance metastasis in oral squamous cell carcinoma (OSCC) was tested.


METHODS
hBD-3 expression in human tissue specimens was evaluated by RT-qPCR and immunohistochemical staining. The presence of hBD-3 peptide in the culture supernatants of each type of treated cells was evaluated by enzyme-linked immunosorbent assay. The chemotaxis response to LPS or hBD-3 protein of SCC-25 cells or siRNA-hBD-3 transfected cells were also measured by chemotaxis assay. Paired, 2-tailed Student t test and analysis of variance was used to assess the statistical significance between 2 groups or many groups.


RESULTS
hBD-3 is highly expressed and associated with lymphatic invasion of OSCC. hBD-3 expression and EGFR phosphorylation were markedly upregulated when SCC-25 cells were treated with LPS. When SCC-25 cells were preincubated with EGFR inhibitor or TLR4-neutralizing Ab before LPS stimulation, a decrease in the expression of hBD-3 was observed. hBD-3 markedly enhanced cancer metastasis, and the chemotaxis response to LPS of SCC-25 cells was partly blocked by siRNA target hBD-3.


CONCLUSIONS
These findings indicate that hBD-3 is upregulated by LPS via EGFR signaling pathways to enhance lymphatic invasion of OSCC.
Shenzhen PKU-HKUST Medical Center, Shenzhen, China.
Yu
Y
Shuyi
Wang
W
Feng
Tang
T
Jing
Huang
H
Hongzhang
Wang
W
Haiyan
Ma
M
Pingping
Zheng
Z
Liwu
Roger A
RA
Zwahlen
Yang
Y
Hongyu
D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000473:pathology*; D002633:Chemotaxis / Q000187:drug effects; D066246:ErbB Receptors / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D008070:Lipopolysaccharides / Q000378:metabolism / Q000494:pharmacology; D042583:Lymphangiogenesis / Q000187:drug effects / Q000502:physiology*; D008207:Lymphatic Metastasis; D009062:Mouth Neoplasms / Q000276:immunology / Q000473:pathology*; D009361:Neoplasm Invasiveness; D015398:Signal Transduction / Q000276:immunology / Q000502:physiology; D014407:Tumor Cells, Cultured; D023083:beta-Defensins / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*
C422950:DEFB103A protein, human; D008070:Lipopolysaccharides; D023083:beta-Defensins; D066246:ErbB Receptors