Glucan from<i> Oudemansiella raphanipes</i> suppresses breast cancer proliferation and metastasis by regulating macrophage polarization and the WNT/β-catenin signaling pathway

Alitongbieke, Gulimiran; Zhang, Xiuru; Zhu, Fukai; Wu, Qici; Lin, Zhichao; Li, Xiumin; Xue, Yu; Lai, Xuebin; Feng, Jiexin; Huang, Rongjie; Pan, Yutian

doi:10.7150/jca.89873

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J Cancer 2024; 15(5):1169-1181. doi:10.7150/jca.89873 This issue Cite

Research Paper

Glucan from Oudemansiella raphanipes suppresses breast cancer proliferation and metastasis by regulating macrophage polarization and the WNT/β-catenin signaling pathway

Gulimiran Alitongbieke^1✉#, Xiuru Zhang^1#, Fukai Zhu^1#, Qici Wu¹, Zhichao Lin¹, Xiumin Li¹, Yu Xue¹, Xuebin Lai¹, Jiexin Feng², Rongjie Huang³, Yutian Pan^1✉

1. Engineering Technological Center of Mushroom Industry, Minnan Normal University, Zhangzhou, Fujian 363000, People's Republic of China.
2. Department of Breast Surgery, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian 363099, People's Republic of China.
3. Department of General Surgery, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian 363099, People's Republic of China.
^# These authors contribute equally to this work.

Citation:

Alitongbieke G, Zhang X, Zhu F, Wu Q, Lin Z, Li X, Xue Y, Lai X, Feng J, Huang R, Pan Y. Glucan from Oudemansiella raphanipes suppresses breast cancer proliferation and metastasis by regulating macrophage polarization and the WNT/β-catenin signaling pathway. J Cancer 2024; 15(5):1169-1181. doi:10.7150/jca.89873. https://www.jcancer.org/v15p1169.htm

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Abstract

Background: The glucan extract of Oudemansiella raphanipes (Orp) has multiple biological properties, similar to extracts of other natural edible fungi. Drugs traditionally used in cancer treatment are associated with several drawbacks, such as side effects, induction of resistance, and poor prognosis, and many recent studies have focused on polysaccharides extracted from natural sources as alternatives. Our study focuses on the therapeutic role and molecular mechanism of action of Orp in breast cancer progression.

Methods: MMTV-PyMT transgenic mice were used as the spontaneous breast cancer mice model. Immunoblotting, hematoxylin-eosin staining, immunohistochemistry, and immunofluorescence were used to evaluate the tumor behaviors in breast cancer. The inflammatory cell model was constructed using TNF-α. Macrophage activation and WNT/β-catenin signaling were assayed using western blotting and immunofluorescence.

Results: Orp management significantly inhibited tumor growth and promoted tumor cell apoptosis in MMTV-PyMT transgenic mice. Besides, the Orp challenge also attenuated the ability of breast tumors to metastasize into lung tissues. Mechanistically, Orp treatment restrained the polarization of M1 macrophages to M2 macrophages and suppressed WNT/β-catenin signaling in mouse tumor tissues, which implied that Orp-mediated tumor inhibition partly occurred via regulating the inflammatory response. Findings from in vitro experiments confirmed that Orp inhibited the TNF-α-induced nuclear transportation of β-catenin, thus preventing inflammation signaling and the expression of c-Myc in MCF-7 cells.

Conclusion: Orp inhibits breast cancer growth and metastasis by regulating macrophage polarization and the WNT/β-catenin signaling axis. The findings of this study suggest that Orp may be a promising therapeutic strategy for breast cancer.

Keywords: Orp, breast cancer, macrophage polarization, WNT/β-catenin signaling pathway, inflammation

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APA

Alitongbieke, G., Zhang, X., Zhu, F., Wu, Q., Lin, Z., Li, X., Xue, Y., Lai, X., Feng, J., Huang, R., Pan, Y. (2024). Glucan from Oudemansiella raphanipes suppresses breast cancer proliferation and metastasis by regulating macrophage polarization and the WNT/β-catenin signaling pathway. Journal of Cancer, 15(5), 1169-1181. https://doi.org/10.7150/jca.89873.

ACS

Alitongbieke, G.; Zhang, X.; Zhu, F.; Wu, Q.; Lin, Z.; Li, X.; Xue, Y.; Lai, X.; Feng, J.; Huang, R.; Pan, Y. Glucan from Oudemansiella raphanipes suppresses breast cancer proliferation and metastasis by regulating macrophage polarization and the WNT/β-catenin signaling pathway. J. Cancer 2024, 15 (5), 1169-1181. DOI: 10.7150/jca.89873.

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CSE

Alitongbieke G, Zhang X, Zhu F, Wu Q, Lin Z, Li X, Xue Y, Lai X, Feng J, Huang R, Pan Y. 2024. Glucan from Oudemansiella raphanipes suppresses breast cancer proliferation and metastasis by regulating macrophage polarization and the WNT/β-catenin signaling pathway. J Cancer. 15(5):1169-1181.

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