Format

Send to:

Choose Destination
See comment in PubMed Commons below
Carcinogenesis. 2011 Feb;32(2):168-74. doi: 10.1093/carcin/bgq236. Epub 2010 Nov 11.

Human β-defensin 3 promotes NF-κB-mediated CCR7 expression and anti-apoptotic signals in squamous cell carcinoma of the head and neck.

Author information

  • 1Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.

Abstract

The microenvironment of aerodigestive cancers contains tumor-promoting inflammatory signals often involved in innate immunity. The epithelial malignancy, squamous cell carcinoma of the head and neck (SCCHN), is characterized by secretion of inflammatory mediators that can promote tumorigenesis and lymph node metastasis. Human β-defensin (hBD) 3 is one such antimicrobial mediator of innate immunity produced by squamous epithelial cells in response to tissue damage and inflammation. Here, we hypothesized that the observed overexpression of hBD3 in SCCHN may have a tumor-promoting effect or contribute to nodal metastasis, which has previously been linked to chemokine receptor (CCR) 7 overexpression. Indeed, treatment of non-metastatic SCCHN cells with hBD3 induced surface CCR7 expression and migration toward its ligand, CCL19. The hBD3-induced CCR7 upregulation in SCCHN cells was significantly reduced by inhibition of nuclear factor (NF)-κB, an inflammatory transcription factor known to influence CCR7 expression. Moreover, hBD3 stimulation provided anti-apoptotic signals to SCCHN cells, as evidenced by tumor resistance to cisplatin-induced cell death, which was regulated by phosphoinositide-3-kinase/Akt activation. Interestingly, the observed hBD3-mediated effects were not dependent on G-protein coupled receptors or toll-like receptors, as has been previously published, but hBD3 was internalized through endocytosis, allowing intracellular signal transduction. Our findings suggest that hBD3 represents a novel NF-κB-regulated mediator of CCR7 expression and anti-apoptotic pathways, which may be exploited by developing SCCHN tumors to enhance their survival and metastasis.

PMID:
21071608
[PubMed - indexed for MEDLINE]
PMCID:
PMC3026843
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk