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 language | English |
|---|---|
| Pages (from-to) | 2615-2623 |
| Number of pages | 9 |
| Journal | Anticancer Research |
| Volume | 30 |
| Issue number | 7 |
| Publication status | Published - Jul 2010 |
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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 journal › Article
}
TY - JOUR
T1 - Bone destruction by invading oral squamous carcinoma cells mediated by the transforming growth factor-β signalling pathway
AU - Goda, Takeshi
AU - Shimo, Tsuyoshi
AU - Yoshihama, Yasuto
AU - Hassan, Nur Mohammad Monsur
AU - Ibaragi, Soichiro
AU - Kurio, Naito
AU - Okui, Tatsuo
AU - Honami, Tatsuki
AU - Kishimoto, Koji
AU - Sasaki, Akira
PY - 2010/7
Y1 - 2010/7
N2 - 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.
AB - 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.
KW - Mandibular bone destruction
KW - Osteoclast
KW - TGF-β
UR - http://www.scopus.com/inward/record.url?scp=77955797385&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77955797385&partnerID=8YFLogxK
M3 - Article
C2 - 20682990
AN - SCOPUS:77955797385
VL - 30
SP - 2615
EP - 2623
JO - Anticancer Research
JF - Anticancer Research
SN - 0250-7005
IS - 7
ER -