Selective inhibition of NF-κB suppresses bone invasion by oral squamous cell carcinoma in vivo

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

研究成果: Contribution to journalArticle査読

22 被引用数 (Scopus)

抄録

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, antiapoptotic 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. Immunohistochemical 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.

本文言語英語
ページ(範囲)E625-E635
ジャーナルInternational Journal of Cancer
131
5
DOI
出版ステータス出版済み - 9 1 2012

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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