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Selective inhibition of NF-κB suppresses bone invasion by oral squamous cell carcinoma in vivo.
MedLine Citation:
PMID:  22262470     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Nuclear factor-κB (NF-κB) is constitutively activated in many cancers, including oral squamous cell carcinoma (OSCC), and is involved in the invasive characteristics of OSCC, such as growth, anti-apoptotic activity and protease production. However, the cellular mechanism underlying NF-κB's promotion of bone invasion by OSCC is unclear. Therefore, we investigated the role of NF-κB in bone invasion by OSCC in vivo. Immnunohistochemical staining of OSCC invading bone in 10 patients indicated that the expression and nuclear translocation of p65, a main subunit of NF-κB, was increased in OSCC compared with normal squamous epithelial cells. An active form of p65 phosphorylated at serine 536 was present mainly in the nucleus in not only differentiated tumor cells but also tumor-associated stromal cells and bone-resorbing osteoclasts. We next injected mouse OSCC SCCVII cells into the masseter region of C3H/HeN mice. Mice were treated for 3 weeks with a selective NF-κB inhibitor, NBD peptide, which disrupts the association of NF-κB essential modulator (NEMO) with IκB kinases. NBD peptide treatment inhibited TNFα-induced and constitutive NF-κB activation in SCCVII cells in vitro and in vivo, respectively. Treatment with NBD peptide decreased zygoma and mandible destruction by SCCVII cells, reduced number of osteoclasts by inhibiting RANKL expression in osteoblastic cells and SCCVII cells, increased apoptosis and suppressed the proliferation of SCCVII cells. Taken together, our data clearly indicate that inhibition of NF-κB is useful for inhibiting bone invasion by OSCC. © 2012 Wiley-Liss, Inc.
Authors:
Hiroyuki Furuta; Kenji Osawa; Masashi Shin; Ayataka Ishikawa; Kou Matsuo; Masud Khan; Kazuhiro Aoki; Keiichi Ohya; Masato Okamoto; Kazuhiro Tominaga; Tetsu Takahashi; Osamu Nakanishi; Eijiro Jimi
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-1-19
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  -     ISSN:  1097-0215     ISO Abbreviation:  -     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-1-20     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 Wiley-Liss, Inc.
Affiliation:
Division of Molecular Signaling and Biochemistry, Department of Bioscience, Kyushu Dental College, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, 803-8580 Fukuoka, Japan; Division of Dental Anesthesiology, Department of Control of Physical Functions, Kyushu Dental College, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, 803-8580 Fukuoka, Japan.
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