Establishment of a murine model of bone invasion by oral squamous cell carcinoma

Nomura, Takeshi; Shibahara, Takahiko; Katakura, Akira; Matsubara, Shizuka; Takano, Nobuo

doi:10.1016/j.oraloncology.2006.03.015

Cited by 28 publications

(41 citation statements)

References 9 publications

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“…Several osteotropic factors/resorption stimuli including 1,25-(OH) 2 D 3 , parathyroid hormone (PTH), IL-1β, IL-11, and prostaglandin E2 have been shown to up-regulate RANKL expression on marrow stromal/osteoblast cells (23)(24)(25). OSCC showed mRNA expression of osteotropic cytokines such as IL-6, tumor necrosis factor α, and PTHrP (26). Therefore, RANKL expression in OSCC cells could be regulated through complex autocrine transcriptional regulatory mechanisms operative in tumor cells.…”

Section: Discussionmentioning

confidence: 99%

A Novel Function of CXCL13 to Stimulate RANK Ligand Expression in Oral Squamous Cell Carcinoma Cells

Sambandam

Griffin

Sundaram

et al. 2009

Molecular Cancer Research

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Oral squamous cell carcinomas (OSCC) are malignant tumors with a potent activity of local bone invasion/ osteolysis. The chemokine ligand, CXCL13, has been identified as a prognostic marker for OSCC development and progression. Here in, we show that recombinant hCXCL13 treatment of OSCC cells stimulates (5-fold) RANK ligand (RANKL), a critical bone resorbing osteoclastogenic factor expression. Anti-CXCR5 chemokine receptor antibody abrogates CXCL13-induced RANKL expression in these cells. Also, CXCL13 stimulated (3.0-fold) hRANKL gene promoter activity in SCC14a cells. SuperArray screening for transcription factors by real-time RT-PCR identified significant increase in the levels of c-Jun and NFATc3 mRNA expression in CXCL13-stimulated OSCC cells. CXCL13 treatment significantly increased (3.5-fold) phospho-c-Jun levels in these cells and a c-Jun-NH 2 -kinase inhibitor abolished CXCL13-stimulated RANKL expression. Furthermore, we show that CXCL13 stimulation induced nuclear translocation of NFATc3 in OSCC cells. Chromatinimmune precipitation assay confirmed NFATc3 binding to the RANKL promoter region. We also show that overexpression of NFATc3 stimulates RANKL expression/ promoter activity and that siRNA suppression of NFATc3 abolished CXCL13-stimulated RANKL expression. Thus, our results suggest that NFATc3 is a downstream target of the CXCL13/CXCR5 axis to stimulate RANKL expression in OSCC cells and implicates CXCL13 as a potential therapeutic target to prevent OSCC bone invasion/

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Section: Discussionmentioning

confidence: 99%

A Novel Function of CXCL13 to Stimulate RANK Ligand Expression in Oral Squamous Cell Carcinoma Cells

Sambandam

Griffin

Sundaram

et al. 2009

Molecular Cancer Research

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“…Nude mice (BALB/cA Jc1 nu/nu) were injected with HNSCC cells and control or RANKL-expressing HSC-3 cells in their muscles in masseter or hindlimb regions. Of note, the masseter region is one of the established sites for an oral cancer orthotopic model, [31][32][33] and the hindlimb region was chosen as a muscle existing far from the oral tissue. Total RNA from developed tumors was isolated using the RNeasy mini kit (Qiagen, Valencia, CA) and was analyzed as described above (under RNA Isolation and PCR).…”

Section: In Vivo Tumor Formation In Nude Micementioning

confidence: 99%

“…To test this possibility, HSC-3 cells were inoculated into the masseter muscles of mice (one of the established sites for a head and neck cancer orthotopic model), [31][32][33] and the amount of RANKL mRNA was analyzed by RT-PCR and qPCR using a primer set specific for human RANKL. As expected, human RANKL expression in all tumor tissues tested (n ϭ 3) was dramatically augmented, compared with cultured control cells ( Figure 2, A and B).…”

Section: Environment-dependent Expression Of Ranklmentioning

confidence: 99%

RANKL Expression Specifically Observed in Vivo Promotes Epithelial Mesenchymal Transition and Tumor Progression

Yamada

Tsuda

Takahashi

et al. 2011

The American Journal of Pathology

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Recent findings have focused attention on the molecular consequences of the microenvironment in tumor progression, but events occurring in cancer cells themselves in response to their ambient conditions remain obscure. Here, we identify receptor activator of nuclear factor B ligand (RANKL) as a microenvironment-specific factor essential for tumorigenesis in vivo, using head and neck squamous cell carcinoma (HNSCC) as a model. In human HNSCC tissues, RANKL is abundantly expressed, and its expression level correlates with the histological grade of differentiation. RANKL levels are significantly higher in poorly differentiated SCCs than in well or moderately differentiated SCCs. In contrast, all HNSCC cell lines tested displayed extremely low RANKL expression; however, RANKL is efficiently up-regulated when these cell lines are inoculated in the head and neck region of mice. RANKL expression is restored in a microenvironment-specific manner, and cannot be observed when the cells are inoculated in the hindlimbs. Forced expression of RANKL compensates for tumor growth in the hindlimb milieu, promotes epithelial mesenchymal transition, and induces tumor angiogenesis, in a manner independent of vascular endothelial growth factor (VEGF). These results implicate RANKL expression causatively in tumor growth and progression in HNSCC in vivo. RANKL may provide a novel functional marker for biological malignancy and a therapeutic target based on the specific nature of the microenvironment.

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“…To test the aforementioned hypothesis, several OSCC cell lines were inoculated into the masseter muscles of mice, one of the most established sites for an oral cancer orthotopic model (Cui et al, 2005;Nomura et al, 2007;Suda et al, 1997). As expected, RANKL expression was dramatically augmented at both mRNA and protein levels compared to those in cultured cells ( Figure 1B).…”

Section: Environment-dependent Expression Of Ranklmentioning

confidence: 68%

“…Therefore, plasma PTHrP level can be a predictor of existence of bone metastatic lesions in a wide range of tumors. PTHrP produced by cancer cells promotes malignant conversion (increased cell proliferation, survival, adhesion, migration, and invasion) of breast, colon, and prostate cancers (Shen et al, 2004), as well as OSCC (Nomura et al, 2007). Because OSCC expresses the PTH/PTHrP receptor PTH1R, its mechanism of action is in a paracrine or autocrine manner (Yamada et al, 2008).…”

Section: Parathyroid Hormone-related Protein (Pthrp)mentioning

confidence: 99%

Functional Biomarkers of Oral Cancer

Tsuda¹,

Ohba²

2012

Oral Cancer

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Establishment of a murine model of bone invasion by oral squamous cell carcinoma

Abstract: Running title: murine model of bone invasion

Cited by 28 publications

References 9 publications

A Novel Function of CXCL13 to Stimulate RANK Ligand Expression in Oral Squamous Cell Carcinoma Cells

A Novel Function of CXCL13 to Stimulate RANK Ligand Expression in Oral Squamous Cell Carcinoma Cells

RANKL Expression Specifically Observed in Vivo Promotes Epithelial Mesenchymal Transition and Tumor Progression

Functional Biomarkers of Oral Cancer

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