Bone destruction by invading oral squamous carcinoma cells mediated by the transforming growth factor-β signalling pathway

Takeshi Goda, Tsuyoshi Shimo, Yasuto Yoshihama, Nur Mohammad Monsur Hassan, Soichiro Ibaragi, Naito Kurio, Tatsuo Okui, Tatsuki Honami, Koji Kishimoto, Akira Sasaki

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Background: Gingival squamous cell carcinoma (SCC) cells frequently invade mandibular bone, and this destruction is associated with a worse prognosis. However, the relationship between bone destruction and associated factors is unclear. In this study, the role and diagnostic utility of transforming growth factor-β (TGF-β) type I receptor (TβRI) in bone destruction of the mandible was investigated. Patients and Methods: The expression of TβRI was explored by using an immunohistochemical method on paraffin-embedded tissues from 21 cases of mandibular SCC. An inhibitor of the kinase activity of the TβRI (TβRI-I) was used to assess the role of TβRI in bone destruction by a human oral SCC cell line (HSC-2) that highly expresses TβRI. Results: TβRI-positive signals were closely associated with destructive invasion of the mandible by oral SCC cells. Consistent with these results, TβRI-I greatly reduced HSC-2 cell-induced bone destruction and osteoclast formation in vivo and in vitro. TβRI-I treatment reduced the expression of TNF-α, RANKL and connective tissue growth factor (CTGF/CCN2), all of which were up-regulated by TGF-β in HSC-2 cells. Conclusion: These data demonstrated an important role for TGF-β signalling in bone invasion by oral SCC cells, and suggest that the bone destruction is mediated by RANKL, TNF-α and CCN2.

Original languageEnglish
Pages (from-to)2615-2623
Number of pages9
JournalAnticancer Research
Volume30
Issue number7
Publication statusPublished - Jul 2010

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Transforming Growth Factors
Squamous Cell Carcinoma
Bone and Bones
Mandible
Connective Tissue Growth Factor
Growth Factor Receptors
Osteoclasts
Paraffin
Phosphotransferases
Cell Line

Keywords

  • Mandibular bone destruction
  • Osteoclast
  • TGF-β

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Bone destruction by invading oral squamous carcinoma cells mediated by the transforming growth factor-β signalling pathway. / Goda, Takeshi; Shimo, Tsuyoshi; Yoshihama, Yasuto; Hassan, Nur Mohammad Monsur; Ibaragi, Soichiro; Kurio, Naito; Okui, Tatsuo; Honami, Tatsuki; Kishimoto, Koji; Sasaki, Akira.

In: Anticancer Research, Vol. 30, No. 7, 07.2010, p. 2615-2623.

Research output: Contribution to journalArticle

Goda, Takeshi ; Shimo, Tsuyoshi ; Yoshihama, Yasuto ; Hassan, Nur Mohammad Monsur ; Ibaragi, Soichiro ; Kurio, Naito ; Okui, Tatsuo ; Honami, Tatsuki ; Kishimoto, Koji ; Sasaki, Akira. / Bone destruction by invading oral squamous carcinoma cells mediated by the transforming growth factor-β signalling pathway. In: Anticancer Research. 2010 ; Vol. 30, No. 7. pp. 2615-2623.
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