2021 Fiscal Year Final Research Report
Novel ex vivo pulmonary metastasis model toward effective suppression of chemotherapeutic-resistant pediatric sarcoma
| Project/Area Number |
19K09043
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 55010:General surgery and pediatric surgery-related
|
|---|
| Research Institution | Osaka University |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
奥山 宏臣 大阪大学, 医学系研究科, 教授 (30252670)
田附 裕子 大阪大学, 医学系研究科, 准教授 (10397698)
塚田 遼 大阪大学, 医学部附属病院, 医員 (70838747)
|
|---|
| Project Period (FY) |
2019-04-01 – 2022-03-31
|
| Keywords | Wnt/beta-cateninシグナル / 癌幹細胞 / 抗癌剤抵抗性 / 小児悪性固形腫瘍 / 肺転移 / Ex vivo肺転移モデル |
|---|
| Outline of Final Research Achievements |
Osteosarcoma(OS) is the most common bone cancer in children and adolescents, and patients with metastatic disease still have extremely poor prognosis. It has been reported that the activation of Wnt/β-catenin pathway is closely associated with OS development and metastatic progression. Tegavivint, a novel small molecule inhibitor of the Wnt/β-catenin pathway, has been reported to be active against multiple types of adult cancer cells in vitro, and antitumor efficacy has been published in animal models of acute myeloid leukemia and multiple myeloma. In this study, we investigated the antitumor activity of Tegavivint against metastatic OS both in vitro and in vivo using established human OS cell lines and patient-derived xenograft(PDX) models. Furthermore, we investigated how the Wnt/β-catenin pathway is activated in lung metastatic sites by employing 3D ex vivo pulmonary metastasis assay(PuMA) model using PDX tumors derived from the relapsed metastatic lung lesion after chemotherapy.
|
| Free Research Field |
小児外科、小児悪性固形腫瘍、分子標的治療
|
| Academic Significance and Societal Importance of the Research Achievements |
骨肉腫などに代表される小児期に発生する肉腫は、多剤併用化学療法の進歩によって予後は大きく改善してきたが、転移を伴うものは、集学的治療をもってしても未だに予後が悪い。よって、転移に関わる因子の同定およびその制御が、予後改善のために非常に重要である。本研究では、肺転移巣内における肉腫の増殖過程およびWnt/βカテニン経路の関与をex vivo肺転移モデルにて可視化し、その制御が癌幹細胞に及ぼす影響についても検討した。これらの成果は、治療抵抗性を示す骨肉腫患者に対する新たな治療法の展望を拓くものであり、学術的意義および社会的意義は高いものと思われる。
|
