The cellular and molecular mechanisms of bone invasion by oral squamous cell carcinoma

Jimi, Eijiro; Furuta, Haruhiko; Matsuo, Keitaro; Tominaga, Kazuhiro; Takahashi, Tsuneo; Nakanishi, Osamu

doi:10.1111/j.1601-0825.2010.01781.x

Cited by 90 publications

(92 citation statements)

References 53 publications

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“…1C) (3). Although controversial, bone destruction that occurs with oral SCC invasion is thought to be mediated by osteoclasts rather than by the carcinoma itself (5).…”

Section: Introductionmentioning

confidence: 99%

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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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“…1C) (3). Although controversial, bone destruction that occurs with oral SCC invasion is thought to be mediated by osteoclasts rather than by the carcinoma itself (5).…”

Section: Introductionmentioning

confidence: 99%

“…Although oral SCC represents 1-2% of all human malignancies in Japan, it is the sixth most common cancer worldwide, with more than 500,000 new cases diagnosed each year. The most common sites for SCCs are the tongue and gingiva (1)(2)(3).…”

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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“…Esses fatores supra-citados formam um pool consensual entre a grande maioria dos pesquisadores (Leite;Koifman, 1998;Gonzáles-Moles et al, 2002;Vicente et al, 2002;Ferlito et al, 2003;Genden et al, 2003;Greenberg et al, 2003;Guerra et al, 2003;O-Charoeniat et al, 2003;Ribeiro et al, 2003;Noolgar et al, 2003;Woolgar et al, 2003;Bettenford et al, 2004;Takes, 2004) Em particular, a extensão óssea do CEMO o classifica no estágio T4a, o que é considerado um fator importante de mau-prognóstico (Jimi et al, 2011).…”

Section: Diagnóstico E Estágios Clínicosunclassified

“…Pacientes com evidência clínica e imaginológica de invasão óssea devem ser tratados cirurgicamente, com ressecção da área acometida(geralmente a mandíbula) (Jimi et al, 2011).…”

Section: Diagnóstico E Estágios Clínicosunclassified

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Aspectos da E-caderina na invasão óssea do carcinoma epidermóide da mucosa oral

Toledo¹

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Selective inhibition of NF‐κB suppresses bone invasion by oral squamous cell carcinoma in vivo

Furuta

Osawa

Shin

et al. 2012

Intl Journal of Cancer

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Nuclear factor-jB (NF-jB) is constitutively activated in many cancers, including oral squamous cell carcinoma (OSCC), and is involved in the invasive characteristics of OSCC, such as growth, antiapoptotic activity and protease production. However, the cellular mechanism underlying NF-jB's promotion of bone invasion by OSCC is unclear. Therefore, we investigated the role of NF-jB in bone invasion by OSCC in vivo. Immunohistochemical staining of OSCC invading bone in 10 patients indicated that the expression and nuclear translocation of p65, a main subunit of NF-jB, was increased in OSCC compared with normal squamous epithelial cells. An active form of p65 phosphorylated at serine 536 was present mainly in the nucleus in not only differentiated tumor cells but also tumor-associated stromal cells and bone-resorbing osteoclasts. We next injected mouse OSCC SCCVII cells into the masseter region of C 3 H/HeN mice. Mice were treated for 3 weeks with a selective NF-jB inhibitor, NBD peptide, which disrupts the association of NF-jB essential modulator (NEMO) with IjB kinases. NBD peptide treatment inhibited TNFa-induced and constitutive NF-jB activation in SCCVII cells in vitro and in vivo, respectively. Treatment with NBD peptide decreased zygoma and mandible destruction by SCCVII cells, reduced number of osteoclasts by inhibiting RANKL expression in osteoblastic cells and SCCVII cells, increased apoptosis and suppressed the proliferation of SCCVII cells. Taken together, our data clearly indicate that inhibition of NF-jB is useful for inhibiting bone invasion by OSCC.Oral squamous cell carcinoma (OSCC) is the most common malignant tumor of the oral cavity, head and neck. 1-3 Despite advances in our understanding of the molecular mechanisms of tumor development, prevention and treatment, the longterm survival for patients with OSCC, a cancer that, worldwide, accounts for more than 500,000 cases each year, 1 remains low. The poor prognosis for OSCC reflects a limited understanding of the mechanisms of local and regional invasion and metastasis present in a significant portion of patients, together with an unsatisfactory responsiveness to conventional systemic therapy in recurrent and advanced disease. 2,3 The ability of OSCC to invade the maxilla or mandibular bone is a critical factor, which, because it leads to metastasis, affects the prognosis of patients. 4 Although controversial, bone destruction that occurs with OSCC invasion is thought to be mediated by osteoclasts rather than by the carcinoma itself. 4 Recent studies have established that bone resorption by osteoclasts is an important step in the process of bone invasion and metastasis in several types of malignancy, 5 indicating that a full understanding of the regulation of osteoclastogenesis by OSCC cells is necessary to prevent bone invasion by OSCC cells. Several in vitro and animal experiments using human OSCC cells have shown that tumor cells

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The cellular and molecular mechanisms of bone invasion by oral squamous cell carcinoma

Cited by 90 publications

References 53 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

Aspectos da E-caderina na invasão óssea do carcinoma epidermóide da mucosa oral

Selective inhibition of NF‐κB suppresses bone invasion by oral squamous cell carcinoma in vivo

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