Polarization of breast cancer-associated macrophages by intratumoral sex-steroids
| Project/Area Number |
16K08645
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Human pathology
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 乳癌 / マクロファージ / アンドロゲン / 浸潤能 / 癌 / 免疫 |
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| Outline of Final Research Achievements |
It has been reported that macrophages express androgen receptors. Therefore, we focused on the relationship between cancer-associated macrophages and intratumoral androgen in breast cancer tissues. Immunohistochemistry demonstrated that androgen receptors were expressed in breast cancer-associated macrophages. Macrophage infiltration was correlated with shorter disease-free and breast cancer-specific survival, especially in the cases positive for androgen-producing enzymes. When we treated THP-1-delived macrophages with R1881, synthetic androgens, expression of CC motif chemokine 5 (CCL5) was significantly increased. Furthermore, recombinant CCL5 significantly promoted invasion of MCF-7 breast cancer cell line.
We therefore concluded that breast cancer-associated macrophages expressed androgen receptor and androgen-induced CCL5 by macrophages caused invasion, angiogenesis and distant metastasis of breast cancer patients.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究はアンドロゲン受容体が乳癌組織浸潤マクロファージに発現することを初めて明らかにし、マクロファージの悪性形質においてアンドロゲンが重要であることを示した。これはが間質細胞におけるアンドロゲンの重要性を示唆する重要な知見である。また、その分子メカニズムとしてCCL5の発現誘導による浸潤能の亢進が示唆され、CCL5が乳癌の治療標的となる可能性が示唆された。
一方、マクロファージの浸潤は様々な固形腫瘍においてみられ、腫瘍内アンドロゲン合成は前立腺癌や子宮内膜癌でも報告されている。したがって、本研究の知見はこれらの腫瘍においても応用可能と考えられ、横断的な研究という発展性を示すことができた。
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Report
(4 results)
Research Products
(30 results)
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[Journal Article] The reduction of heparan sulphate in the glomerular basement membrane does not augment urinary albumin excretion2018
Author(s)
Satoshi Aoki, Akiko Saito-Hakoda, Takeo Yoshikawa, Kyoko Shimizu, Kiyomi Kisu, Susumu Suzuki, Kiyoshi Takagi, Shuji Mizumoto, Shuhei Yamada, Toin H. van Kuppevelt, Atsushi Yokoyama, Taiji Matsusaka, Hiroshi Sato, Sadayoshi Ito, and Akira Sugawara
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Journal Title
Nephrology Dialysis Transplantation
Volume: 33
Issue: 1
Pages: 26-33
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Hexokinase 2 in colorectal cancer: a potent prognostic factor associated with glycolysis, proliferation and migration2017
Author(s)
Katagiri M, Karasawa H, Takagi K, Nakayama S, Yabuuchi S, Fujishima F, Naitoh T, Watanabe M, Suzuki T, Unno M, Sasano H
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Journal Title
Histol Histopathol.
Volume: 32
Pages: 351-360
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] CITED2 in breast carcinoma as a potent prognostic predictor associated with proliferation, migration and chemoresistance2016
Author(s)
Minemura H, Takagi K, Sato A, Takahashi H, Miki Y, Shibahara Y, Watanabe M, Ishida T, Sasano H, Suzuki T.
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Journal Title
Cancer Sci.
Volume: 107
Issue: 12
Pages: 1898-1908
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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