Redefining cervical adenocarcinoma as estrogen-dependent cancer
Project/Area Number |
20K07409
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 49020:Human pathology-related
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Research Institution | Sapporo Medical University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
秋元 太志 札幌医科大学, 医学部, 助教 (20815435)
青山 智志 札幌医科大学, 医学部, 研究員 (50737781)
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Project Status |
Completed (Fiscal Year 2022)
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Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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Keywords | 子宮頸部 / 子宮頸部腺がん / エストロゲン / 細胞接着 / GPR30 / 比較プロテオーム解析 / がん微小環境 / GPER1 / 子宮頸がん / エストロゲン受容体 |
Outline of Research at the Start |
本研究では、従来、エストロゲン非依存性として理解されてきた頸部腺がんが、エストロゲン依存性がんであることを再定義し、それに基づき頸部腺がんの新たな治療戦略の提言を目指す。その達成のため、頸部腺がんにおいて①エストロゲン関連刺激が腫瘍に及ぼす効果、②多層オミクス解析によりエストロゲン関連刺激の分子メカニズム、③ヒトパピローマウイルス(HPV)感染とGPR30の関連、を明らかにする。
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Outline of Final Research Achievements |
In cervical adenocarcinoma, ER expression was not associated with prognosis, and the high expression group of the membrane estrogen receptor GPR30 had a poor prognosis. In cell lines with a deletion of claudin-1, which expression is regulated by estrogen-GPR30, the expression of cell adhesion molecules was suppressed and the cell morphology was affected. In the cervical adenocarcinoma cell line, we identified several proteins that are upregulated in an estrogen-dependent manner and are intensely involved in the malignant transformation of cancer. ER-positive CAFs were recognized around cervical adenocarcinomas, and cervical adenocarcinomas with strong stromal response had a significantly poor prognosis, suggesting a contribution of estrogen to the cancer microenvironment. Estrogen was suggested to be involved in the malignant transformation of cervical adenocarcinoma via several cells and cascades.
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Academic Significance and Societal Importance of the Research Achievements |
子宮頸部腺がんは増加傾向にあり、若年者で予後不良を示すことが問題となっている。また、通常型の頸部腺がんは、ER発現が陰性であり、エストロゲンの悪性化への関与はほとんど議論されてこなかった。我々は頸部腺がんで膜型エストロゲン受容体GPR30が高発現し、エストロゲン依存性を示すことを初めて明らかにし、その機序の解析を行った。その結果、エストロゲンで発現誘導される複数のタンパク質が悪性化に関与していることを確認した。更に、がん微小環境に関与している可能性を見出した。本研究成果により、頸部腺がんの悪性化機序の理解が深まり、患者の治療戦略の再構築へ向けた知見を得ることができた。
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Report
(4 results)
Research Products
(51 results)
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[Journal Article] Serum amyloid A1 recruits neutrophils to the invasive front of T1 colorectal cancers.2023
Author(s)
Yoshido A, Sudo G, Takasawa A, Aoki H, Kitajima H, Yamamoto E, Niinuma T, Harada T, Kubo T, Sasaki H, Ishiguro K, Yorozu A, Kai M, Katanuma A, Yamano HO, Osanai M, Nakase H, Suzuki H.
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Journal Title
J Gastroenterol Hepatol.
Volume: 38
Issue: 2
Pages: 301-310
DOI
Related Report
Peer Reviewed
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[Journal Article] CXCL12 is expressed by skeletal muscle cells in tongue oral squamous cell carcinoma.2023
Author(s)
Yorozu A, Sekiguchi S, Takasawa A, Okazaki F, Niinuma T, Kitajima H, Yamamoto E, Kai M, Toyota M, Hatanaka Y, Nishiyama K, Ogi K, Dehari H, Obata K, Kurose M, Kondo A, Osanai M, Miyazaki A, Takano K, Suzuki H.
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Journal Title
Cancer Med.
Volume: 12
Issue: 5
Pages: 5953-5963
DOI
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Peer Reviewed / Open Access
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[Journal Article] COVID-19-associated disseminated mucormycosis: An autopsy case report2022
Author(s)
Kyuno Daisuke、Kubo Terufumi、Tsujiwaki Mitsuhiro、Sugita Shintaro、Hosaka Michiko、Ito Hazuki、Harada Keisuke、Takasawa Akira、Kubota Yusaku、Takasawa Kumi、Ono Yusuke、Magara Kazufumi、Narimatsu Eichi、Hasegawa Tadashi、Osanai Makoto
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Journal Title
World Journal of Clinical Cases
Volume: 10
Issue: 28
Pages: 10358-10365
DOI
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Peer Reviewed / Open Access
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[Journal Article] Aberrant expression of junctional adhesion molecule-A contributes to the malignancy of cervical adenocarcinoma by interaction with poliovirus receptor/CD155.2021
Author(s)
Murakami T, Takasawa A, Takasawa K, Akimoto T, Aoyama T, Magara K, Saito Y, Ota M, Kyuno D, Yamamoto S, Hasegawa T, Saito T, Osanai M.
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Journal Title
Cancer Science
Volume: 112
Issue: 2
Pages: 906-917
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Aldolase A promotes epithelial-mesenchymal transition to increase malignant potentials of cervical adenocarcinoma.2020
Author(s)
Saito Y, Takasawa A, Takasawa K, Aoyama T, Akimoto T, Ota M, Magara K, Murata M, Hirohashi H, Hasegawa T, Sawada N, Saito T, Osanai M.
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Journal Title
Cancer Science
Volume: 111
Issue: 8
Pages: 3071-3081
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Aberrant high expression of ALDOA contributes to the malignant transformation of uterine cervical adenocarcinoma2021
Author(s)
Akira Takasawa, Yuki Saito, Kumi Takasawa, Taishi Akimoto, Kazufumi Magara, Tomoyuki Aoyama, Yusuke Ono, Daisuke Kyuno, Yoshihiko Hirohashi, Tsuyoshi Saito, Makoto Osanai.
Organizer
The 39th Sapporo International Cancer Symposium
Related Report
Int'l Joint Research
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[Presentation] Clinical usefulness of SMOC1 as a diagnostic marker of colorectal precancerous lesions and colorectal cancers2021
Author(s)
Hironori Aoki, Eiichiro Yamamoto, Akira Takasawa, Takeshi Niinuma, Hiro-o Yamano, Akira Yorozu, Hiroshi Kitajima, Masahiro Kai, Makoto Osanai, Hiroshi Nakase, Tamotsu Sugai, Hiromu Suzuki
Organizer
第80回日本癌学会学術総会
Related Report
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