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Plasma exosomes from endometrial cancer patients contain LGALS3BP to promote endometrial cancer progression

Abstract

Endometrial cancer (EC) is a common gynaecological cancer worldwide. Exosomes, secreted by living cells and detected in various body fluids, can exchange information between organs and compartments to affect cellular functions, such as proliferation, apoptosis, migration and angiogenesis. We hypothesise that plasma exosomal contents are altered during cancer progression and promote cancer growth and angiogenesis by delivering biomolecules to cancer and vascular endothelial cells. In this study, circulating exosomes derived from EC patients and age-matched healthy people were acquired by commercial kits. Cell counting kit-8, Transwell and Matrigel tube formation assays showed that circulating exosomes from EC patients promote EC cell growth and human umbilical vein endothelial cell (HUVEC) angiogenesis. Next, proteomic analysis and ELISA revealed that plasma exosomal lectin galactoside-binding soluble 3 binding protein (LGALS3BP) increased during EC progression. Moreover, to explore the function of exosomal LGALS3BP, we acquired exosomes containing high levels of LGALS3BP by overexpressing LGALS3BP in human embryonic kidney 293 cells, and we demonstrated that highly contained exosomal LGALS3BP contributed to EC cell proliferation and migration and HUVEC functions via the activation of the PI3K/AKT/VEGFA signalling pathway both in vitro and in vivo. Finally, high LGALS3BP expression was observed in human EC tissue, which indicated a poor prognosis. In addition, immunohistochemical analysis of human EC tissues revealed that LGALS3BP expression was correlated with VEGFA expression and blood vessel density. Hence, we proposed that plasma exosomes containing LGALS3BP contributed to EC growth and angiogenesis during EC progression, which also provided a novel perspective on EC diagnosis and prognosis.

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Fig. 1: Exosomes from EC patients promoted EC cell proliferation, migration and HUVEC angiogenesis.
Fig. 2: Analysis of TMT-labelled proteomics results and correlation of differentially expressed protein levels of LGALS3BP in plasma exosomes with EC progression.
Fig. 3: Exosomes loaded with a large amount of LGALS3BP contribute to EC cell growth and vascular angiogenesis.
Fig. 4: Exosomes enriched with LGALS3BP contribute to cancer cell growth and angiogenesis via the activation of the PI3K/AKT/VEGFA signalling pathway.
Fig. 5: The role of exosomal LGALS3BP in tumour growth and angiogenesis in a xenograft model.
Fig. 6: The LGALS3BP expression level was high in EC patients’ cancer tissue and associated with VEGFA expression and CD31-positive vessel density, indicating a poor prognosis.

Data availability

All the data and techniques within the article and Supplementary Information file are available from the corresponding author upon reasonable request.

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Acknowledgements

This work was supported by Shanghai Science and Technology Commission Innovation Plan (No. 17411951600), the National Natural Science Foundation of China (Nos. 81672574 and 81972438) and Shanghai Key Clinical Specialty Programme (No. 2017ZZ02015).

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Correspondence to Kai Wang or Xiaoping Wan.

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Song, Y., Wang, M., Tong, H. et al. Plasma exosomes from endometrial cancer patients contain LGALS3BP to promote endometrial cancer progression. Oncogene 40, 633–646 (2021). https://doi.org/10.1038/s41388-020-01555-x

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