Analysis of lipid metabolism via LSR and anti-tumor effect of anti-LSR antibody in ovarian cancer
| Project/Area Number |
19K16748
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 50010:Tumor biology-related
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| Research Institution | Osaka University |
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Principal Investigator |
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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 |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
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| Keywords | 卵巣癌 / LSR / 子宮体癌 |
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| Outline of Research at the Start |
卵巣癌は進行癌として診断されることが多く、手術・抗癌剤治療は困難を極める。申請者らは卵巣癌細胞のタンパク質発現解析を行い、lipolysis-stimulated lipoprotein receptor (LSR) を同定し、この高発現が卵巣癌の予後不良因子であることを発見した。さらに新規に抗LSR抗体を作成し、この抗体が卵巣癌細胞株およびヒト卵巣癌組織移植マウスモデルに抗腫瘍効果を示すことを証明した。しかしLSRの役割と抗LSR抗体の作用機序はまだ十分に解明されていない。本研究では卵巣癌の増殖・生存・播種にLSRが如何に関わるか、抗LSR抗体が何を阻害するのかを分子生物学的に解析する
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| Outline of Final Research Achievements |
(1) LSR expression in LSR-positive cells was higher in hypoxic environment and glucose deprivation compared with normal culture. (3) LDL and VLDL did not induce cell migration of LSR-positive cells.
(4) In endometrial cancer which is one of the gynecologic cancer same as ovarian cancer, high expression of LSR was significantly poor prognostic factor. Especially, LSR strongly related to myometrial invasion and distant metastasis. LSR promoted MAPK pathway and subsequent cell proliferation. Furthermore, LSR promoted expression of MMP2 and Mt1-MMP which are related to EMT and contributed cell invasion. Finally, anti-LSR antibody inhibited theses processes.
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| Academic Significance and Societal Importance of the Research Achievements |
卵巣癌においてLSRは低酸素や低Glcといった環境下での細胞の増殖/生存に関わることが示唆された。また同時に検証した子宮体癌におけるLSRの機能は、卵巣癌と同様に細胞の増殖の促進であり、今回新たにEMTに関連するMMP2の発現がLSRと関連することが証明され、LSRが卵巣癌と子宮体癌の増殖、浸潤、遊走に深くかかわることが示唆された。
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Report
(4 results)
Research Products
(15 results)
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[Presentation] Lipolysis-stimulated lipoprotein receptor regulates cell proliferation and invasion, and associates with poor prognosis in endometrial cancer.2021
Author(s)
Yoshikazu Nagase, Kosuke Hiramatsu, Masashi Funauchi, Mayu Shiomi, Tatsuo Masuda, Satoshi Nakagawa, Shinya Matsuzaki, Eiji Kobayashi, Toshihiro Kimura, Yutaka Ueda, Tetsuji Naka, Tadashi Kimura.
Organizer
第62回日本婦人科腫瘍学会学術講演会
Related Report
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[Presentation] LSR is a novel prognostic factor by regulating cell proliferation via MEK/ERK pathway in endometrial cancer: Analysis of signal transduction, bioinformatics, and in vitro/in vivo study2021
Author(s)
Yoshikazu Nagase, Kosuke Hiramatsu, Satoshi Nakagawa, Shinya Matsuzaki, Toshihiro Kimura, Satoshi Serada, Yutaka Ueda, Tetsuji Naka, Tadashi Kimura.
Organizer
AACR ANNUAL MEETING 2021
Related Report
Int'l Joint Research
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[Presentation] LSR is a novel therapeutic target via cell proliferation and invasion in endometrial cancer: analysis of signal transduction, bioinformatics, and in vitro/in vivo study2021
Author(s)
Yoshikazu Nagase, Kosuke Hiramatsu, Masashi Funauchi, Mayu Shiomi, Tatsuo Masuda, Satoshi Nakagawa, Shinya Matsuzaki, Eiji Kobayashi, Toshihiro Kimura, Yutaka Ueda, Tetsuji Naka, Tadashi Kimura.
Organizer
第73回日本産科婦人科学会学術講演会
Related Report
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[Presentation] LSR promotes tumor progression by regulating signal transduction of apoptosis and ferroptosis in endometrial cancer2021
Author(s)
Yoshikazu Nagase, Kosuke Hiramatsu, Masashi Funauchi, Satoshi Nakagawa, Shinya Matsuzaki, Eiji Kobayashi, Toshihiro Kimura, Satoshi Serada, Yutaka Ueda, Tetsuji Naka, Tadashi Kimura.
Organizer
22nd European Congress on Gynaecological Oncology of ESGO
Related Report
Int'l Joint Research
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[Presentation] LSR in endometrial cancer: A novel prognostic factor by regulating cell proliferation and invasion via MEK/ERK pathway2020
Author(s)
Yoshikazu Nagase, Kosuke Hiramatsu, Masashi Funauchi, Mayu Shiomi, Satoshi Nakagawa, Shinya Matsuzaki, Eiji Kobayashi, Toshihiro Kimura, Yutaka Ueda, Tetsuji Naka, Tadashi Kimura
Organizer
第79回日本癌学会学術総会
Related Report
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[Presentation] Lipolysis-stimulated lipoprotein receptor regulates cell proliferation and invasion, and associates with poor prognosis in endometrial cancer.2020
Author(s)
Yoshikazu Nagase, Kosuke Hiramatsu, Masashi Funauchi, Satoshi Nakagawa, Shinya Matsuzaki, Eiji Kobayashi, Toshihiro Kimura, Yutaka Ueda, Tetsuji Naka, Tadashi Kimura
Organizer
第62回日本婦人科腫瘍学会学術講演会
Related Report
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