A study of osteoclast-related cytokines in mandibular invasion by squamous cell carcinoma

Shibahara, Takahiko; Nomura, Takeshi; Cui, Nian-Hui; Noma, Hiroyasu

doi:10.1016/j.ijom.2005.03.008

Cited by 36 publications

(46 citation statements)

References 23 publications

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“…2) (13). Shibahara et al have reported that the invasive tumors showed a high level of expression of IL-6, IL-11, TNFα and PTHrP (14). In contrast, expression of TGF-β, IL-1α/β and IL-18 were not different between invasive and non-invasive tumors, suggesting that various cancer-derived cytokines, such as IL-6, IL-11, TNFα and PTHrP, play important roles in bone invasion by oral SCC (14).…”

Section: Introductionmentioning

confidence: 99%

The RANKL/RANK system as a therapeutic target for bone invasion by oral squamous cell carcinoma

Jimi

Shin

Furuta

et al. 2013

International Journal of Oncology

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Abstract. Squamous cell carcinomas (SCCs) of the gingiva frequently invade the mandible or maxilla; this invasion is associated with a worse prognosis. The bone destruction associated with carcinomal invasion is mediated by osteoclasts rather than directly by the carcinoma. Therefore, if the cellular and molecular mechanisms by which oral SCC regulates bone invasion were known, it could inform the development of new therapeutic targets. Recently, dysregulation of the functional equilibrium in the receptor activator of NF-κB ligand (RANKL)/RANK/osteoprotegerin (OPG) triad has been shown to be responsible for osteolysis associated with the development of malignant tumors in bone sites. Furthermore, the administration of OPG or soluble RANK prevents bone metastasis by cancer cells. In this review, we discuss recent findings indicating that bone invasion by oral SCC is mediated via RANKL/RANK and may be successfully prevented by RANKL inhibition.

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Section: Introductionmentioning

confidence: 99%

The RANKL/RANK system as a therapeutic target for bone invasion by oral squamous cell carcinoma

Jimi

Shin

Furuta

et al. 2013

International Journal of Oncology

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“…High levels of expression of PTHrP mRNA and protein were observed in these SCCVII cells, as is seen in patients with OSCC with bone invasion (21). We generated stable PTHrP knock-down cells by RNA interference technology using retroviral vectors in order to evaluate the role of PTHrP in bone invasion.…”

Section: Discussionmentioning

confidence: 98%

“…PTHrP is a major mediator of osteoclast activity (24) and clinical analyses have suggested that osteoclast activation factors, including PTHrP, are highly expressed in patients with OSCC with bone invasion (21).…”

Section: Discussionmentioning

confidence: 99%

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

Takayama

Mori²,

Nomura

et al. 2010

Int J Oncol

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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-ß (TGF-ß) in PTHrP-mediated bone invasion. TGF-ß 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-ß appears to act synergistically to accelerate mandibular bone invasion.

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“…Once breast cancer metastases are established in bone or lung, the condition is generally con.sidered incurable. There is therefore an urgent need to improve current therapies that address cancer spread, and an ideal solution will target upstream signaling molecules to prevent compensatory mechanisms that can result from blockade of individual downscream signaling points (3,4).…”

Section: Introductionmentioning

confidence: 99%

Osteoblast-Derived PTHRP and Breast Cancer Bone Metastasis

Karaplis¹

2004

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. REPORT DATE November 2004 REPORT TYPE PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES). McGill University Montreal, Canada H3A2T5 Metastases to bone, l ur:g, and other organs are common and catastrophic consequences of breast cancer progression. There is therefore an urgent need to improve current therapies I that address cancer grm.,th and spread. PERFORMING ORGANIZATION REPORT NUMBER SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR'S ACRONYM(S)UParathyroid hormone-related protein (PTHrP, also referred to as parathyroid hormone-like protein [PTHLP]) is a secreted factor expressed in almost all normal fetal and adult tissues, acting as an autocrine, paracrine, or intracrine factor in a wide range of developmental and physiological processes. Although PTHrP's dysregulated expression has traditionally been associated with oncogenic pathologies as the major causative agent of malignancy-associated hypercalcemia, recent evidence revealed a driving role in skeletal metastasis progression. Here, we demonstrate that PTHrP is also closely involved in breast cancer initiation, growth and metastasis to bone and lung through mechanisms separate from its bone turnover action, and we suggest that PTHrP as facilitator of oncogenes could serve as a novel target for therapeutic intervention. SUBJECT TERMS INTRODUCTIONParathyroid hormone-related protein (PTHrP) is a secreted factor expressed in almost all normal fetal and adult tissues. It is involved in a wide range of developmental and physiological processes, including serum calcium regulation. PTHrP is also associated with the progression of skeletal metastases, and its dysregulated expression in advanced cancers causes malignancyassociated hypercalcemia. Although PTHrP is frequently expressed by breast tumors and other solid cancers, its involvement in tumor initiation and metastasis in vivo is not clear. BODYPTHrP is expressed in normal epithelial cells but its expression increases in breast cancer and becomes associated with multiple metastatic lesions and reduced survival. It is, however, still unknown whether PTHrP overexpression is simply a con...

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A study of osteoclast-related cytokines in mandibular invasion by squamous cell carcinoma

Cited by 36 publications

References 23 publications

The RANKL/RANK system as a therapeutic target for bone invasion by oral squamous cell carcinoma

The RANKL/RANK system as a therapeutic target for bone invasion by oral squamous cell carcinoma

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

Osteoblast-Derived PTHRP and Breast Cancer Bone Metastasis

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