M6PR- and EphB4-Rich Exosomes Secreted by Serglycin-Overexpressing Esophageal Cancer Cells Promote Cancer Progression

Yan, Dongdong; Cui, Di; Zhu, Yun; Chan, Cecilia Ka Wing; Choi, Chung Hang Jonathan; Liu, Tengfei; Lee, Nikki P.Y.; Law, Simon; Tsao, Sai Wah; Ma, Stephanie; Cheung, Annie Lai Man

doi:10.7150/ijbs.79875

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International Journal of Medical Sciences

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Int J Biol Sci 2023; 19(2):625-640. doi:10.7150/ijbs.79875 This issue Cite

Research Paper

M6PR- and EphB4-Rich Exosomes Secreted by Serglycin-Overexpressing Esophageal Cancer Cells Promote Cancer Progression

Dongdong Yan¹, Di Cui¹, Yun Zhu², Cecilia Ka Wing Chan³, Chung Hang Jonathan Choi³, Tengfei Liu¹, Nikki P.Y. Lee⁴, Simon Law⁴, Sai Wah Tsao¹, Stephanie Ma^1,5, Annie Lai Man Cheung^1✉

1. School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong SAR, China.
2. Center for Clinical Big Data and Analytics, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
3. Department of Biomedical Engineering, The Chinese University of Hong Kong, Hong Kong SAR, China.
4. Department of Surgery, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong SAR, China.
5. The University of Hong Kong - Shenzhen Hospital, Shenzhen, China.

Citation:

Yan D, Cui D, Zhu Y, Chan CKW, Choi CHJ, Liu T, Lee NPY, Law S, Tsao SW, Ma S, Cheung ALM. M6PR- and EphB4-Rich Exosomes Secreted by Serglycin-Overexpressing Esophageal Cancer Cells Promote Cancer Progression. Int J Biol Sci 2023; 19(2):625-640. doi:10.7150/ijbs.79875. https://www.ijbs.com/v19p0625.htm

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Abstract

Accumulating evidence shows that exosomes participate in cancer progression. However, the functions of cancer cell exosome-transmitted proteins are rarely studied. Previously, we reported that serglycin (SRGN) overexpression promotes invasion and metastasis of esophageal squamous cell carcinoma (ESCC) cells. Here, we investigated the paracrine effects of exosomes from SRGN-overexpressing ESCC cells (SRGN Exo) on ESCC cell invasion and tumor angiogenesis, and used mass spectrometry to identify exosomal proteins involved. Cation-dependent mannose-6-phosphate receptor (M6PR) and ephrin type-B receptor 4 (EphB4) were pronouncedly upregulated in SRGN Exo. Upregulated exosomal M6PR mediated the pro-angiogenic effects of SRGN Exo both in vitro and in vivo, while augmented exosomal EphB4 mediated the pro-invasive effect of SRGN Exo on ESCC cells in vitro. In addition, in vitro studies showed that manipulation of M6PR expression affected the viability and migration of ESCC cells. Both M6PR and EphB4 expression levels were positively correlated with that of SRGN in the serum of patients with ESCC. High level of serum M6PR was associated with poor overall survival rates. Taken together, this study presents the first proof that exosomal M6PR and EphB4 play essential roles in tumor angiogenesis and malignancy, and that serum M6PR is a novel prognostic marker for ESCC patients.

Keywords: Exosome, M6PR, EphB4, serglycin, angiogenesis, invasion

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APA

Yan, D., Cui, D., Zhu, Y., Chan, C.K.W., Choi, C.H.J., Liu, T., Lee, N.P.Y., Law, S., Tsao, S.W., Ma, S., Cheung, A.L.M. (2023). M6PR- and EphB4-Rich Exosomes Secreted by Serglycin-Overexpressing Esophageal Cancer Cells Promote Cancer Progression. International Journal of Biological Sciences, 19(2), 625-640. https://doi.org/10.7150/ijbs.79875.

ACS

Yan, D.; Cui, D.; Zhu, Y.; Chan, C.K.W.; Choi, C.H.J.; Liu, T.; Lee, N.P.Y.; Law, S.; Tsao, S.W.; Ma, S.; Cheung, A.L.M. M6PR- and EphB4-Rich Exosomes Secreted by Serglycin-Overexpressing Esophageal Cancer Cells Promote Cancer Progression. Int. J. Biol. Sci. 2023, 19 (2), 625-640. DOI: 10.7150/ijbs.79875.

NLM

CSE

Yan D, Cui D, Zhu Y, Chan CKW, Choi CHJ, Liu T, Lee NPY, Law S, Tsao SW, Ma S, Cheung ALM. 2023. M6PR- and EphB4-Rich Exosomes Secreted by Serglycin-Overexpressing Esophageal Cancer Cells Promote Cancer Progression. Int J Biol Sci. 19(2):625-640.

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