Functional analysis of uterine cancer stem cell-associated protein SPARC and development of novel drugs targeting it
Project/Area Number |
19H03800
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Review Section |
Basic Section 56040:Obstetrics and gynecology-related
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Research Institution | Kyushu University |
Principal Investigator |
kato kiyoko 九州大学, 医学研究院, 教授 (10253527)
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Co-Investigator(Kenkyū-buntansha) |
片山 佳樹 九州大学, 工学研究院, 教授 (70284528)
森 健 九州大学, 工学研究院, 准教授 (70335785)
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Project Status |
Completed (Fiscal Year 2021)
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Budget Amount *help |
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2021: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2019: ¥8,450,000 (Direct Cost: ¥6,500,000、Indirect Cost: ¥1,950,000)
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Keywords | 子宮体癌 / 癌幹細胞 / SPARC / AKT / Aldoxorubicin / がん幹細胞 / SAPRC |
Outline of Research at the Start |
本研究では、secreted proteins acidic and rich in cysteine (以下SPARC)を「子宮体癌がん幹細胞関連蛋白」としてとらえ、1)その発現機構を脱メチル化の点から解析し、また活性化の分子機構をMMP3の点から検討するとともに、2)SPARCが腫瘍細胞や間質細胞などの周囲の微小環境へ及ぼす影響やその相互作用を明らかにする。また、3)SPARCがアルブミン結合蛋白である性質を利用し、SPARCを標的とするアルブミン結合薬剤を創薬し子宮体癌の新規治療法を開発する。
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Outline of Final Research Achievements |
We examined the function of SPARC, which is upregulated in uterine cancer stem cells. We showed that SPARC expression in endometrial cancer cells induces phosphorylation of AKT and epithelial-mesenchymal transition, and that SPARC activates fibroblasts in the presence of fibronectin. Furthermore, after confirming the binding and cellular uptake of SPARC to fluorescently labeled human serum albumin, we confirmed the growth inhibitory effect of albumin-bound doxorubicin, Aldoxorubicin, on SPARC-expressing uterine cancer cells in three-dimensional culture and in vivo. These results indicate that Aldoxorubicin is a potential therapeutic candidate for the treatment of SPARC-expressing uterine cancer in the future.
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Academic Significance and Societal Importance of the Research Achievements |
子宮体癌において、進行癌や再発・転移例は予後不良であり治療抵抗性のがんの克服が課題である。治療抵抗性の要因として、がん幹細胞の存在が言われており、がん幹細胞を標的とした新規治療法の開発が急務である。我々は幹細胞の同定法の一つであるSide-population細胞を分離する方法を用いて子宮体がん幹細胞の解析を行い、EMTが治療抵抗性の重要な因子であること、このEMTにはSPARCとfibronectinの共発現が関与していることを明らかにした。このSPARCやfibronectinを標的とした治療法が開発は悪性度の高い子宮体癌の予後改善に貢献でき社会的に意義がある。
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Report
(4 results)
Research Products
(42 results)
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[Journal Article] YBX2 and cancer testis antigen 45 contribute to stemness, chemoresistance and a high degree of malignancy in human endometrial cancer2021
Author(s)
Suzuki I, Yoshida S, Tabu K, Kusunoki S, Matsumura Y, Izumi H, Asanoma K, Yagi H, Onoyama I, Sonoda K, Kohno K, Taga T, Itakura A, Takeda S, Kato K
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Journal Title
Scientific Reports
Volume: 11
Issue: 1
Pages: 4220-4220
DOI
NAID
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Peer Reviewed / Open Access
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[Journal Article] Mutual suppression between BHLHE40/BHLHE41 and the MIR301B-MIR130B cluster is involved in epithelial-to-mesenchymal transition of endometrial cancer cells2019
Author(s)
Asanoma K, Hori E, Yoshida S, Yagi H, Onoyama I, Kodama K, Yasunaga M, Ohgami T, Kaneki E, Okugawa K, Yahata H, Kato K,
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Journal Title
Oncotarget
Volume: 10
Issue: 45
Pages: 4640-4654
DOI
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Peer Reviewed / Open Access
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[Presentation] 早期子宮頸癌におけるセンチネルノードナビゲーション手術の長期予後2021
Author(s)
矢幡 秀昭, 川上 穣, 蜂須賀 一寿, 安武 伸子, 小玉 敬亮, 八木 裕史, 大神 達寛, 安永 昌史, 小野山 一郎, 奥川 馨, 淺野間 和夫, 加藤 聖子
Organizer
第59回日本癌治療学会学術集会
Related Report
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[Presentation] International Session Poster 5 Cervical Cancer/CIN/SIL 3(Group 5); No adjuvant therapy for intermediate-risk group of cervical cancer after radical hysterectomy2019
Author(s)
Yahata H, Inoue S, Kijima M, Yamaguchi S, Yagi H, Yasunaga M, Ohgami T, Onoyama I, Kaneki E, Okugawa K, Kato K
Organizer
第71回日本産科婦人科学会学術講演会
Related Report
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[Presentation] International Session Workshop 5 Oncology 2 Ovarian Cancer 1(Group 5); GEP oncogene induces epithelial-mesenchymal transition in ovarian cancer through LATS1 proteolysis2019
Author(s)
Yahata H, Inoue S, Kijima M, Yamaguchi S, Yagi H, Yasunaga M, Ohgami T, Onoyama I, Kaneki E, Okugawa K, Kato K
Organizer
第71回日本産科婦人科学会学術講演会
Related Report
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[Presentation] International Session Poster 31 Endometrial Cancer 3(Group 31); FRZB, Wnt inhibitor, functions as a tumor suppressor gene at early stage of carcinogenesis in endometrial cancer2019
Author(s)
Onoyama I, Yasunaga M, Kodama K, Inoue S, Yamaguchi S, Yagi H , Ohgami T, Kaneki E, Okugawa K, Asanoma K, Yahata H, Kato K
Organizer
第71回日本産科婦人科学会学術講演会
Related Report
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[Presentation] International Session Poster 32 Cervical Cancer/CIN/SIL 4(Group 32); Retrospective evaluation of cervical laser vaporization for cervical intraepithelial neoplasia in our institution2019
Author(s)
Kodama K, Kijima M , Inoue S, Yamaguchi S, Yagi H, Yasunaga M, Tatsuhiro , Onoyama I, Kaneki K, Okugawa K, Yahata H, Kato K
Organizer
第71回日本産科婦人科学会学術講演会
Related Report
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[Presentation] International Session Workshop 6 Oncology 3 Cervical Cancer/CIN/SIL2(Group 6); Safety evaluation of abdominal trachelectomy in patients with cervical cancer with tumors 2 cm:A single-institution, retrospective analysis2019
Author(s)
Okugawa K, Inoue S, Kodama K, Yamaguchi S, Kenjo H, Yagi H, Ohgami T, Yasunaga M, Onoyama I, Kaneki E, Yahata H, Kato K
Organizer
第71回日本産科婦人科学会学術講演会
Related Report
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[Presentation] Is adjuvant therapy necessary for cervical cancer patients with intermediate risk factors after radical hysterectomy?2019
Author(s)
Yahata H, Inoue S, Kijima M, Yamaguchi S, Yagi H, Yasunaga M, Ogami T, Onoyama I, Kaneki E, Okugawa K, Asanoma K, Kato K
Organizer
The 26thAsia and Oceania Federation of Obstetrics and Gynaecology Congress (AOFOG)
Related Report
Int'l Joint Research
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[Book] 女性ヘルスケア2019
Author(s)
加藤聖子、藤井知行
Total Pages
384
Publisher
中山書店
ISBN
9784521747668
Related Report