Parathyroid-related protein plays a critical role in bone invasion by oral squamous cell carcinoma

Yuki Takayama, Taisuke Mori, Takeshi Nomura, Takahiko Shibahara, Michiie Sakamoto

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Bone invasion is a critical prognostic factor for patients with oral squamous cell carcinoma (OSCC). We established an orthotropic implantation model using the murine OSCC cell line, SCCVII, showing direct invasion of the mandible by OSCC. Using this model, we examined the molecular mechanisms of bone invasion and the role of parathyroid-related protein (PTHrP). We established PTHrP, stable, knock-down SCCVII cells. Knock-down of PTHrP caused decreased osteoclast formation in vitro relative to expression levels of PTHrP. In vivo models showed dramatic suppression of bone invasion in PTHrP knock-down cells, and the degree of suppression was more pronounced than the level of PTHrP knock-down. We looked at an additive role of transforming growth factor-β (TGF-β) in PTHrP-mediated bone invasion. TGF-β induced mRNA expression of PTHrP, showed no inhibitory effect on SCCVII cell proliferation, and caused epithelial mesenchymal trans-differentiation such as changes in the cells. Sections of resected mandibles from patients with invasive OSCC showed a great number of osteoclasts at bone invasion sites, strong expression of PTHrP, and decreased expression of E-cadherin in the tumour cells. Cancer-derived PTHrP appears to play a critical role in bone invasion by OSCC, mediated by osteoclasts. Moreover, TGF-β appears to act synergistically to accelerate mandibular bone invasion.

Original languageEnglish
Pages (from-to)1387-1394
Number of pages8
JournalInternational Journal of Oncology
Volume36
Issue number6
DOIs
Publication statusPublished - 2010 Jun

Fingerprint

Squamous Cell Carcinoma
Bone and Bones
Proteins
Transforming Growth Factors
Osteoclasts
Mandible
Parathyroid Neoplasms
Molecular Models
Cadherins
Cell Proliferation
Cell Line
Messenger RNA

Keywords

  • Animal model
  • Bone invasion
  • Oral squamous cell carcinoma
  • PTHrP

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Parathyroid-related protein plays a critical role in bone invasion by oral squamous cell carcinoma. / Takayama, Yuki; Mori, Taisuke; Nomura, Takeshi; Shibahara, Takahiko; Sakamoto, Michiie.

In: International Journal of Oncology, Vol. 36, No. 6, 06.2010, p. 1387-1394.

Research output: Contribution to journalArticle

Takayama, Yuki ; Mori, Taisuke ; Nomura, Takeshi ; Shibahara, Takahiko ; Sakamoto, Michiie. / Parathyroid-related protein plays a critical role in bone invasion by oral squamous cell carcinoma. In: International Journal of Oncology. 2010 ; Vol. 36, No. 6. pp. 1387-1394.
@article{65305ec8f7a04cf3b4b8fb22799f3ecf,
title = "Parathyroid-related protein plays a critical role in bone invasion by oral squamous cell carcinoma",
abstract = "Bone invasion is a critical prognostic factor for patients with oral squamous cell carcinoma (OSCC). We established an orthotropic implantation model using the murine OSCC cell line, SCCVII, showing direct invasion of the mandible by OSCC. Using this model, we examined the molecular mechanisms of bone invasion and the role of parathyroid-related protein (PTHrP). We established PTHrP, stable, knock-down SCCVII cells. Knock-down of PTHrP caused decreased osteoclast formation in vitro relative to expression levels of PTHrP. In vivo models showed dramatic suppression of bone invasion in PTHrP knock-down cells, and the degree of suppression was more pronounced than the level of PTHrP knock-down. We looked at an additive role of transforming growth factor-β (TGF-β) in PTHrP-mediated bone invasion. TGF-β induced mRNA expression of PTHrP, showed no inhibitory effect on SCCVII cell proliferation, and caused epithelial mesenchymal trans-differentiation such as changes in the cells. Sections of resected mandibles from patients with invasive OSCC showed a great number of osteoclasts at bone invasion sites, strong expression of PTHrP, and decreased expression of E-cadherin in the tumour cells. Cancer-derived PTHrP appears to play a critical role in bone invasion by OSCC, mediated by osteoclasts. Moreover, TGF-β appears to act synergistically to accelerate mandibular bone invasion.",
keywords = "Animal model, Bone invasion, Oral squamous cell carcinoma, PTHrP",
author = "Yuki Takayama and Taisuke Mori and Takeshi Nomura and Takahiko Shibahara and Michiie Sakamoto",
year = "2010",
month = "6",
doi = "10.3892/ijo-00000623",
language = "English",
volume = "36",
pages = "1387--1394",
journal = "International Journal of Oncology",
issn = "1019-6439",
publisher = "Spandidos Publications",
number = "6",

}

TY - JOUR

T1 - Parathyroid-related protein plays a critical role in bone invasion by oral squamous cell carcinoma

AU - Takayama, Yuki

AU - Mori, Taisuke

AU - Nomura, Takeshi

AU - Shibahara, Takahiko

AU - Sakamoto, Michiie

PY - 2010/6

Y1 - 2010/6

N2 - Bone invasion is a critical prognostic factor for patients with oral squamous cell carcinoma (OSCC). We established an orthotropic implantation model using the murine OSCC cell line, SCCVII, showing direct invasion of the mandible by OSCC. Using this model, we examined the molecular mechanisms of bone invasion and the role of parathyroid-related protein (PTHrP). We established PTHrP, stable, knock-down SCCVII cells. Knock-down of PTHrP caused decreased osteoclast formation in vitro relative to expression levels of PTHrP. In vivo models showed dramatic suppression of bone invasion in PTHrP knock-down cells, and the degree of suppression was more pronounced than the level of PTHrP knock-down. We looked at an additive role of transforming growth factor-β (TGF-β) in PTHrP-mediated bone invasion. TGF-β induced mRNA expression of PTHrP, showed no inhibitory effect on SCCVII cell proliferation, and caused epithelial mesenchymal trans-differentiation such as changes in the cells. Sections of resected mandibles from patients with invasive OSCC showed a great number of osteoclasts at bone invasion sites, strong expression of PTHrP, and decreased expression of E-cadherin in the tumour cells. Cancer-derived PTHrP appears to play a critical role in bone invasion by OSCC, mediated by osteoclasts. Moreover, TGF-β appears to act synergistically to accelerate mandibular bone invasion.

AB - Bone invasion is a critical prognostic factor for patients with oral squamous cell carcinoma (OSCC). We established an orthotropic implantation model using the murine OSCC cell line, SCCVII, showing direct invasion of the mandible by OSCC. Using this model, we examined the molecular mechanisms of bone invasion and the role of parathyroid-related protein (PTHrP). We established PTHrP, stable, knock-down SCCVII cells. Knock-down of PTHrP caused decreased osteoclast formation in vitro relative to expression levels of PTHrP. In vivo models showed dramatic suppression of bone invasion in PTHrP knock-down cells, and the degree of suppression was more pronounced than the level of PTHrP knock-down. We looked at an additive role of transforming growth factor-β (TGF-β) in PTHrP-mediated bone invasion. TGF-β induced mRNA expression of PTHrP, showed no inhibitory effect on SCCVII cell proliferation, and caused epithelial mesenchymal trans-differentiation such as changes in the cells. Sections of resected mandibles from patients with invasive OSCC showed a great number of osteoclasts at bone invasion sites, strong expression of PTHrP, and decreased expression of E-cadherin in the tumour cells. Cancer-derived PTHrP appears to play a critical role in bone invasion by OSCC, mediated by osteoclasts. Moreover, TGF-β appears to act synergistically to accelerate mandibular bone invasion.

KW - Animal model

KW - Bone invasion

KW - Oral squamous cell carcinoma

KW - PTHrP

UR - http://www.scopus.com/inward/record.url?scp=77951553897&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77951553897&partnerID=8YFLogxK

U2 - 10.3892/ijo-00000623

DO - 10.3892/ijo-00000623

M3 - Article

C2 - 20428761

AN - SCOPUS:77951553897

VL - 36

SP - 1387

EP - 1394

JO - International Journal of Oncology

JF - International Journal of Oncology

SN - 1019-6439

IS - 6

ER -