Research of the mechanism of bone resorption by the cancer: Comprehensive analysis focusing on the regulation of RANKL expression and osteoclastogenesis.

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K10266
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57060:Surgical dentistry-related
• Research Institution: Hiroshima University (2021-2022); Osaka University (2019-2020)
• Principal Investigator: Aikawa Tomonao 広島大学, 医系科学研究科(歯), 教授 (00362674)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 骨吸収 / 扁平上皮癌 / IL-7 / RANKL / T細胞

Outline of Final Research Achievements

The molecular mechanisms of bone resorption and destruction in squamous cell carcinoma were analyzed using a syngeneic mouse model of cranial bone invasion. Squamous cell carcinoma cell line cells; SCC7-derived high- and low-resorption sub cell line cells were used to analyze gene expression in bone-resorbing and non-bone-resorbing areas by RNA sequencing. We found that interleukin 7 (IL- 7) was the highly expressed soluble factors in the high bone-resorption area. Administration of anti-LI-7 neutralizing antibody to the high bone resorption subline tumors markedly reduced RANKL gene expression, TRAP gene expression, and cathepsin K gene expression in the tumors, and also markedly suppressed bone resorption. The results suggest that IL-7 would be involved in bone resorption by squamous cell carcinoma cells.

Free Research Field

外科系歯学

Academic Significance and Societal Importance of the Research Achievements

多くの癌腫の治療法の確立と治療の向上により、原発巣病変の治癒が向上している。しかしながら、他臓器転移病巣、例えば骨転移などの骨病変に対する治療は困難を極める。口腔扁平上皮癌においては、骨病変の成立機序も明らかにされておらず、治療手法が少ないのが現状である。
本研究は骨浸潤の分子機序を明らかにするという学術的な意義に加え、将来的な口腔扁平上皮癌の骨病変治療の基礎となりうる点で医療的な、社会的な意義も大きい。