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Int J Biol Sci 2023; 19(13):4259-4277. doi:10.7150/ijbs.85986 This issue Cite

Research Paper

Coculture of cancer cells with platelets increases their survival and metastasis by activating the TGFβ/Smad/PAI-1 and PI3K/AKT pathways

Haibo Tong1, Koukou Li1, Muya Zhou1, Renfei Wu1, Hongmei Yang1, Zheng Peng1, Qi Zhao1,2, Kathy Qian Luo1,2✉

1. Faculty of Health Sciences, University of Macau, Taipa, Macao SAR, China.
2. Ministry of Education Frontiers Science Center for Precision Oncology, University of Macau.

✉ Corresponding author: Kathy Qian Luo; E-mail: kluoedu.mo

Citation:
Tong H, Li K, Zhou M, Wu R, Yang H, Peng Z, Zhao Q, Luo KQ. Coculture of cancer cells with platelets increases their survival and metastasis by activating the TGFβ/Smad/PAI-1 and PI3K/AKT pathways. Int J Biol Sci 2023; 19(13):4259-4277. doi:10.7150/ijbs.85986. https://www.ijbs.com/v19p4259.htm
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Abstract

Graphic abstract

When cancer cells enter the bloodstream, they can interact with platelets to acquire stronger survival and metastatic abilities. To elucidate the underlying mechanisms, we cocultured metastatic melanoma and triple-negative breast cancer cells with species-homologous platelets. We found that cocultured cancer cells displayed higher viabilities in circulation, stronger capacities for cell migration, invasion, and colony formation in vitro, and more tumorigenesis and metastasis in mice. RNA sequencing analysis revealed that the level of serpin family E member 1 (SERPINE1) was significantly upregulated in cocultured cancer cells. Knockdown of SERPINE1 reversed the coculture-elevated survival and metastatic phenotypes of cancer cells. Mechanistic studies indicated that coculture with platelets activated the TGFβ/Smad pathway to induce SERPINE1 expression in cancer cells, which encodes plasminogen activator inhibitor 1 (PAI-1). PAI-1 then activated PI3K to increase the phosphorylation of AKTThr308 and Bad to elevate Bcl-2, which enhanced cell survival in circulation. Moreover, higher levels of PAI-1 were detected in metastatic tumors from melanoma and triple-negative breast cancer patients than in normal tissues, and high levels of PAI-1 were associated with a shorter overall survival time and worse disease progression in breast cancer. PAI-1 may act as a potential biomarker for detecting and treating metastatic tumor cells.

Keywords: Cancer cells, platelets, survival, metastasis, TGFβ, PAI-1

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APA
Tong, H., Li, K., Zhou, M., Wu, R., Yang, H., Peng, Z., Zhao, Q., Luo, K.Q. (2023). Coculture of cancer cells with platelets increases their survival and metastasis by activating the TGFβ/Smad/PAI-1 and PI3K/AKT pathways. International Journal of Biological Sciences, 19(13), 4259-4277. https://doi.org/10.7150/ijbs.85986.

ACS
Tong, H.; Li, K.; Zhou, M.; Wu, R.; Yang, H.; Peng, Z.; Zhao, Q.; Luo, K.Q. Coculture of cancer cells with platelets increases their survival and metastasis by activating the TGFβ/Smad/PAI-1 and PI3K/AKT pathways. Int. J. Biol. Sci. 2023, 19 (13), 4259-4277. DOI: 10.7150/ijbs.85986.

NLM
Tong H, Li K, Zhou M, Wu R, Yang H, Peng Z, Zhao Q, Luo KQ. Coculture of cancer cells with platelets increases their survival and metastasis by activating the TGFβ/Smad/PAI-1 and PI3K/AKT pathways. Int J Biol Sci 2023; 19(13):4259-4277. doi:10.7150/ijbs.85986. https://www.ijbs.com/v19p4259.htm

CSE
Tong H, Li K, Zhou M, Wu R, Yang H, Peng Z, Zhao Q, Luo KQ. 2023. Coculture of cancer cells with platelets increases their survival and metastasis by activating the TGFβ/Smad/PAI-1 and PI3K/AKT pathways. Int J Biol Sci. 19(13):4259-4277.

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