| Budget Amount *help |
¥10,640,000 (Direct Cost: ¥10,100,000、Indirect Cost: ¥540,000)
Fiscal Year 2007: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 2005: ¥6,100,000 (Direct Cost: ¥6,100,000)
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| Research Abstract |
The ability of bone invasion of the oral cancer is strongly affected by the bone microenvironment. The purpose of this study is to develop the evaluation model of the cancer bone invasion under the reproduction of bone microenvironment, in which clinical application was possible. 1) Evaluation of Clinical examination: There was no correlation between radiographic bone resorption type and histological invasion in biopsy specimen of the patient with gingival cancer, and there was no the correlation between the bone resorption type and the radiographic bone resorption type as well as the number of osteoclasts adjacent to bone in surgical specimens. However, the expression of TGF-P, TGF-DR significantly increased. 2) In vivo and in vitro evaluation model for the cancer invasion into bones: Various oral squamous cell carcinomas (OSC) were injected into the bone marrow in mice (in vivo model). Various OSC were cultured in the bone extracellular matrix (BECM) with non-collagen protein (IGF-II
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, TGF-β, IGF-I, PDGF, bFGF) (in vitro model). The mRNA expression of bone resorption related factors (PTHrP, OPG, RANKL, RANK, IL-la, IL-6, PGE2, TNF-a, VEGF, CTGF) in vitro model were measured by quantity RT-PCR. As a result, in vitro model showed the manifestation elevation of the bone resorption factors, a manifestation fall tendency of OPG in the HSC-2, -3, and SAS, which showed high bone resorption in vivo model. The conditioned medium from HSC-2, -3 and SAS under the in vitro model significantly promoted the osteoclasts formation. These results suggested that in vitro model could be useful to evaluate the activity of bone invasion. 3) TGF-β is a candidate in of bone resorption marker. Bone invasion cell line HSC-2 implanted at periosteal region, and examined the effect of TβRI-I on bone destruction model. Radiography presented the moss-eaten appearance induced by HSC-2, but the bone invasion was inhibited by TβRI-I. The culture supernatant of HSC-2 of stimulated by TGF-β promoted the osteoclasts formation, and significantly increased the TNF-α, CCN2, RANKL mRNA, but it was inhibited by TβRI-I. These results suggested that TGF-β and the signal transduction of its receptor could be useful bone invasion marker in the evaluation model of the cancer bone invasion, at the same time, could be a target molecule for the treatment of osteolysis by OSC. Less
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