Effect of YM529 on a Model of Mandibular Invasion by Oral Squamous Cell Carcinoma in Mice

Autor: Masato Okamoto, Takeshi Nomura, Sadamitsu Hashimoto, Keiko Yokoo, Hiroyasu Noma, Mitsunobu Sato, Ryo Takagi, Chuan-bin Guo, Takahiko Shibahala, Nian-hui Cui, Guangyan Yu
Rok vydání: 2005
Předmět:
Male
Cancer Research
Pathology
medicine.medical_treatment
Gene Expression
Osteoclasts
Receptors
Cytoplasmic and Nuclear
Mandible
Receptors
Tumor Necrosis Factor
Mice
Receptor
Mice
Inbred C3H
Membrane Glycoproteins
Diphosphonates
Receptor Activator of Nuclear Factor-kappa B
biology
Reverse Transcriptase Polymerase Chain Reaction
Imidazoles
Oncology
RANKL
Carcinoma
Squamous Cell
Mouth Neoplasms
Tumor necrosis factor alpha
medicine.medical_specialty
Imaging
Three-Dimensional
Osteoprotegerin
Cell Line
Tumor
Internal medicine
medicine
Carcinoma
Animals
Neoplasm Invasiveness
RNA
Messenger
Bone Resorption
Glycoproteins
Interleukin-6
Tumor Necrosis Factor-alpha
business.industry
Body Weight
RANK Ligand
Parathyroid Hormone-Related Protein
Acid phosphatase
Bisphosphonate
medicine.disease
Disease Models
Animal
Endocrinology
biology.protein
Carrier Proteins
Tomography
X-Ray Computed
business
Zdroj: Clinical Cancer Research. 11:2713-2719
ISSN: 1557-3265
1078-0432
Popis: Purpose: This study examined the mechanisms of osteoclast-mediated bone invasion in a model of oral squamous cell carcinoma (OSCC). C3H/HeN mice were inoculated with SCC VII cells into the masseter region to establish an animal model of mandibular invasion by OSCC. Experimental Design: The mice were divided into three groups: a control group, given daily s.c. injections of saline; group 1, given 2 μg per mouse per day of the bisphosphonate YM529; and group 2, given 10 μg per mouse per day of YM529. After 3 weeks of treatment, the lesions were studied by micro-computed tomography. After tartrate-resistant acid phosphatase (TRAP) staining, the osteoclasts were easily identified, and the percentages of the area occupied by osteoclasts were calculated by computer for each sample. The tumors were analyzed by RT-PCR to determine the mRNA expression of interleukin-6 (IL-6), parathyroid hormone–related protein (PTHrP), tumor necrosis factor-α (TNF-α), receptor activator of nuclear factor-κB (RANK), RANK ligand (RANKL), and osteoprotegerin. Results: SCC VII cells rapidly multiplied in the masseter muscle of the mice. Bone invasion was evident only in the control group on micro-computed tomography. On TRAP-stained slices, the percentages of osteoclasts in groups 1 and 2 were significantly lower than that in the control group. The mRNA expressions of IL-6, PTHrP, THF-α, and RANK decreased as the concentration of YM529 increased. Conclusions: We conclude that various cancer-derived cytokines play important roles in the invasion of bone by OSCC. YM529, a third-generation bisphosphonate, can suppress osteoclast-mediated bone invasion by OSCC. The mechanism of this effect might involve inhibition of cytokines such as IL-6, PTHrP, TNF-α, and RANK by YM529.
Databáze: OpenAIRE
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