破骨細胞性骨吸収を標的とした癌の骨浸潤・骨破壊制御に関する基礎的研究

• 佐々木 朗

  岡山大学大学院医歯薬学総合研究科歯顎口腔病態外科学分野

書誌事項

タイトル別名

• Investigation of inhibitory therapy of osteoclastic bone resorption for cancer-induced osteolysis
• ハコツ サイボウセイコツ キュウシュウ オ ヒョウテキ ト シタ ガン ノ コツ シンジュン コツ ハカイ セイギョ ニ カンスル キソテキ ケンキュウ

抄録

Cancer-induced osteolysis such as bone invasion or bone metastasis causes serious morbidity and reduces the survival rate or quality of life of cancer patients. Osteoclastic bone resorption plays an important role in cancer-induced bone diseases. Angiogenesis is an essential process in tumor growth and metastasis formation. Recently, it has been reported that a close relationship exists between osteoclastic bone resorption and angiogenic factors. Therefore, it is expected that potent osteoclastic bone resorption inhibitors or anti-angiogenesis agents would be efficacious for cancer-induced osteolysis.<BR>In the present study, we examined the effects of third-generation bisphosphonate as a bone resorption inhibitor, anti-angiogenesis agent TNP-470, matrix metalloproteinase inhibitor against MMP-2 and -9 (MMI-166), and an antibody against connective tissue growth factor (CTGF) as an angiogenesis inhibitor, on an osteolytic bone metastasis model in nude mice. Moreover, the effects of TNP-470 on a hypercalcemia model of nude mice transplanted with a human oral squamous cell carcinoma secreting PTHrP were examined. Consequently, bisphosphonate markedly inhibited the progression of established osteolytic lesions and prevented the development of new osteolytic lesions. TNP-470, an antibody against CTGF, and MMI-166 also inhibited cancerinduced osteolytic lesions in nude mice. TNP-470 also significantly improved the increase of blood Ca²⁺ in the hypercalcemia model. TNP-470 suppressed osteoclast formation and bone resorption activity in vitro. Antisense oligonucleotide of CTGF inhibited osteoclast formation, but did not affect the osteoclast activity. This indicates that anti-angiogenesis might suppress the osteoclastic bone resorption. These results suggested that inhibition of osteoclastic bone resorption has a possibility of therapeutic use for the treatment of cancer-induced bone osteolysis.

収録刊行物

• 日本口腔科学会雑誌

  日本口腔科学会雑誌 55 (1), 1-9, 2006

  特定非営利活動法人 日本口腔科学会

キーワード

• 破骨細胞
• 血管新生
• ビスフォスフォネート
• 骨破壊
• 癌

詳細情報

• CRID: 1390001206437285504
• NII論文ID: 130004335917
• NII論文ID: 10018827458
• NII書誌ID: AN00189050
• DOI: 10.11277/stomatology1952.55.1
• ISSN: 21850461
• ISSN: 00290297
• NDL書誌ID: 7826309
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I7826309
• Web Site: https://search.jamas.or.jp/link/ui/2006086240
• 本文言語コード: ja
• データソース種別:
  • JaLC
  • NDL
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可