Investigation on how mechanical force transducer PIEZO1 controls the polarization of tumor-associated neutrophils and its relationship with colorectal cancer development
DOI:
https://doi.org/10.61173/b619zy48Keywords:
Tumor-associated neutrophils, polarization, Piezo1, colorectal cancer, TGF-βAbstract
Nowadays, during the polarization of neutrophils, the function of the mechanical force transducer PIEZO1 is still unclear. Our research shows that the PIEZO1 gene knockout in tumor-associated neutrophils (TANs) can suppress the polarization of TANs towards the N2 phenotype induced by TGF-β; Activating PIEZO1 by Yoda1 promotes polarization. We discover that cancer cell proliferation is enhanced by coculturing colorectal cancer cells with N2 TANs. On the contrary, when PIEZO1 is knocked out, the cancer development alleviates due to its prevention of TANs polarizing towards N2. Our research hints that mechanical force transducer PIEZO1 might be a new target spot during the treatment of colorectal cancer.
References
[1] Anderson, N. and Simon, M., 2020. The tumor microenvironment. Current Biology, 30(16), pp.R921-R925.
[2] Masucci, M. T., Minopoli, M., & Carriero, M. V. (2019). Tumor-Associated Neutrophils. Their Role in Tumorigenesis, Metastasis, Prognosis and Therapy. Frontiers in Oncology, 9. https://doi.org/10.3389/fonc.2019.01146
[3] Cancer.Net. 2022. Colorectal Cancer - Statistics. [online] Available at:
[4] <https://www.cancer.net/cancer-types/colorectal-cancer/ statistics> [Accessed Sept 10 2022].
[5] Li Tong-Kai, Guo Jian-Sheng. Progress of tumor-associated neutrophils in colorectal cancer [J]. Tumor Research and Clinics, 2021, 33(11): 874-877.
[6] Dean&Francis
[7] Andzinski, L., Kasnitz, N., Stahnke, S., Wu, C., Gereke, M., von Köckritz-Blickwede, M., Schilling, B., Brandau, S., Weiss, S. and Jablonska, J., 2015. Type IIFNs induce antitumor polarization of tumor-associated neutrophils in mice and humans. International Journal of Cancer, 138(8), pp.1982-1993.
[8] Friedlander, Z., Sun, J., Kim, S., Kapoor, V., Cheng, G., Ling, L., Worthen, G. and Albelda, S., 2009. Polarization of Tumor-Associated Neutrophil Phenotype by TGF-β: “N1” versus “N2” TAN. Cancer Cell, 16(3), pp.183-194.
[9] Ma, Y., Yabluchanskiy, A., Iyer, R. P., Cannon, P. L., Flynn, E. R., Jung, M., Henry, J., Cates, C. A., Deleon-Pennell, K. Y., & Lindsey, M. L. (2016). Temporal neutrophil polarization following myocardial infarction. Cardiovascular Research, 110(1), 51–61. https://doi.org/10.1093/cvr/cvw024
[10] Kang, Q., Li, L., Pang, Y., Zhu, W., & Meng, L. (2022). An update on Ym1 and its immunoregulatory role in diseases. Frontiers in Immunology, 13, 891220. https://doi.org/10.3389/ fimmu.2022.891220
[11] Mihaila, A. C., Ciortan, L., Macarie, R. D., Vadana, M., Cecoltan, S., Preda, M. B., Hudita, A., Gan, A.-M., Jakobsson, G., Tucureanu, M. M., Barbu, E., Balanescu, S., Simionescu, M., Schiopu, A., & Butoi, E. (2021). Transcriptional Profiling and Functional Analysis of N1/N2 Neutrophils Reveal an Immunomodulatory Effect of S100A9-Blockade on the Pro- Inflammatory N1 Subpopulation. Frontiers in Immunology, 12. https://doi.org/10.3389/fimmu.2021.708770
[12] Chung, J. Y.-F., Tang, P. C.-T., Chan, M. K.-K., Xue, V. W., Huang, X.-R., Ng, C. S.-H., Zhang, D., Leung, K.-T., Wong, C.- K., Lee, T.-L., Lam, E. W.-F. ., Nikolic-Paterson, D. J., To, K.-F., Lan, H.-Y., & Tang, P. M.-K. (2023). Smad3 is essential for the polarization of tumor-associated neutrophils in non-small cell lung carcinoma. Nature Communications, 14(1), 1794. https:// doi.org/10.1038/s41467-023-37515-8
[13] Jin, J., Lin, J., Xu, A., Lou, J., Qian, C., Li, X., Wang, Y., Yu, W., & Tao, H. (2021). CCL2: An Important Mediator Between Tumor Cells and Host Cells in Tumor Microenvironment. Frontiers in Oncology, 11. https://doi. org/10.3389/fonc.2021.722916
[14] Ma, Y., Yabluchanskiy, A., Iyer, R. P., Cannon, P. L., Flynn, E. R., Jung, M., Henry, J., Cates, C. A., Deleon-Pennell, K. Y., & Lindsey, M. L. (2016b). Temporal neutrophil polarization following myocardial infarction. Cardiovascular Research, 110(1), 51–61. https://doi.org/10.1093/cvr/cvw024
[15] Water Technologies & Solutions. (2020). Water Technologies & Solutions application note determining equivalent onset optical density (OD) values on the Sievers Eclipse* BET platform purpose. https://www.insatech.com/ media/uvyfg34n/art_optical-density-eclipse_300-00092_ed-a_ e.pdf
[16] Syeda, R., Xu, J., Dubin, A. E., Coste, B., Mathur, J., Huynh, T., Matzen, J., Lao, J., Tully, D. C., Engels, I. H., Petrassi, H. M., Schumacher, A. M., Montal, M., Bandell, M., & Patapoutian, A. (2015). Chemical activation of the mechanotransduction channel Piezo1. ELife, 4. https://doi. org/10.7554/elife.07369
[17] Chun, E., Lavoie, S., Michaud, M., Gallini, C., Kim, J., Soucy, G., Odze, R., Glickman, J. and Garrett, W., 2022. CCL2 Promotes Colorectal Carcinogenesis by Enhancing Polymorphonuclear Myeloid-Derived Suppressor Cell Population and Function.
[18] Ohms M, Möller S, Laskay T. An Attempt to Polarize Human Neutrophils Toward N1 and N2 Phenotypes in vitro. Front Immunol. 2020 Apr 28;11:532.
[19] De Felice D, Alaimo A. Mechanosensitive Piezo Channels in Cancer: Focus on altered Calcium Signaling in Cancer Cells and Tumor Progression. Cancers (Basel). 2020 Jul 3;12(7):1780
[20] Atcha, H., Jairaman, A., Holt, J.R. et al. Mechanically activated ion channel Piezo1 modulates macrophage polarization and stiffness sensing. Nat Commun 12, 3256 (2021).
Downloads
Published
Issue
Section
License
Copyright (c) 2023 by the authors.

This work is licensed under a Creative Commons Attribution 4.0 International License.
