Int J Biol Sci 2022; 18(16):5994-6007. doi:10.7150/ijbs.73141 This issue Cite

Research Paper

Tumor-associated macrophages in direct contact with prostate cancer cells promote malignant proliferation and metastasis through NOTCH1 pathway

Fei Shi1,2#, Meng-Hao Sun1,2#, Zheng Zhou3#, Lei Wu3, Zheng Zhu4, Shu-Jie Xia1,2,3, Bang-Min Han1,2, Yu-Yang Zhao1,2✉, Yi-Feng Jing1,2✉, Di Cui1,2✉

1. Department of Urology, Shanghai General Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
2. Institute of Urology, Shanghai Jiao Tong University, Shanghai 200080, China.
3. Department of Urology, Shanghai General Hospital, Nanjing Medical University, Shanghai 200080, China.
4. Department of Internal Medicine, Division of Hematology/Oncology, University of California Davis, Sacramento, CA 95817, USA.
#These authors contributed equally to this work.

Citation:
Shi F, Sun MH, Zhou Z, Wu L, Zhu Z, Xia SJ, Han BM, Zhao YY, Jing YF, Cui D. Tumor-associated macrophages in direct contact with prostate cancer cells promote malignant proliferation and metastasis through NOTCH1 pathway. Int J Biol Sci 2022; 18(16):5994-6007. doi:10.7150/ijbs.73141. https://www.ijbs.com/v18p5994.htm
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Abstract

Graphic abstract

Background: M2 macrophages are well accepted to promote cancer progression in the prostate cancer (PCa). Paracrine is the principally studied mode of communication between M2 macrophages and tumor cells. In addition to this, we present here a novel model to demonstrate these cellular communications.

Methods: PCa cells were co-cultured with THP-1/ human peripheral blood mononuclear cells derived M2 macrophages in direct contact manner. Cancer cell proliferation and invasion were examined to explain how direct contact communicates. Cell-based findings were validated in two xenograft models and patients samples.

Results: M2 macrophage direct contact induced a higher proliferation and invasion in PCa cells when compared with noncontact coculture manner. In direct contact manner, NOTCH1 pathway was greatly activated in PCa cells, induced by elevated γ-secretase activity and higher coactivator MAML2 expression. Additionally, blocking γ-secretase activity and depletion of MAML2 completely abolished M2 macrophage direct contact-mediated PCa cell proliferation and invasion. In vivo, inhibiting NOTCH1 signalling impaired M2 macrophage-mediated PCa tumor growth and lung metastasis. Notably, M2 macrophage infiltration as well as high NOTCH1 signaling in cancer cells indicated more aggressive features and worse survival in PCa patients.

Conclusion: Our results demonstrated the cell-cell direct contact pattern is an important way in PCa microenvironment cell communication. In this manner, elevated γ-secretase activity and MAML2 expression induced higher NOTCH1 signalling in PCa cells, which increased tumor cells proliferation and invasion. This potentially provided a therapeutic target for PCa.

Keywords: prostate cancer (PCa), tumor-associated macrophage (TAM), NOTCH1 signaling, MAML2, cancer progression


Citation styles

APA
Shi, F., Sun, M.H., Zhou, Z., Wu, L., Zhu, Z., Xia, S.J., Han, B.M., Zhao, Y.Y., Jing, Y.F., Cui, D. (2022). Tumor-associated macrophages in direct contact with prostate cancer cells promote malignant proliferation and metastasis through NOTCH1 pathway. International Journal of Biological Sciences, 18(16), 5994-6007. https://doi.org/10.7150/ijbs.73141.

ACS
Shi, F.; Sun, M.H.; Zhou, Z.; Wu, L.; Zhu, Z.; Xia, S.J.; Han, B.M.; Zhao, Y.Y.; Jing, Y.F.; Cui, D. Tumor-associated macrophages in direct contact with prostate cancer cells promote malignant proliferation and metastasis through NOTCH1 pathway. Int. J. Biol. Sci. 2022, 18 (16), 5994-6007. DOI: 10.7150/ijbs.73141.

NLM
Shi F, Sun MH, Zhou Z, Wu L, Zhu Z, Xia SJ, Han BM, Zhao YY, Jing YF, Cui D. Tumor-associated macrophages in direct contact with prostate cancer cells promote malignant proliferation and metastasis through NOTCH1 pathway. Int J Biol Sci 2022; 18(16):5994-6007. doi:10.7150/ijbs.73141. https://www.ijbs.com/v18p5994.htm

CSE
Shi F, Sun MH, Zhou Z, Wu L, Zhu Z, Xia SJ, Han BM, Zhao YY, Jing YF, Cui D. 2022. Tumor-associated macrophages in direct contact with prostate cancer cells promote malignant proliferation and metastasis through NOTCH1 pathway. Int J Biol Sci. 18(16):5994-6007.

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