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Title: Microenvironmental hypoxia induces dynamic changes in lung cancer synthesis and secretion of extracellular vesicles
Authors: Tse, Shun Wilford
Tan, Chee Fan
Park, Jung Eun
Gnanasekaran, JebaMercy
Gupta, Nikhil
Low, Jee Keem
Yeoh, Kheng Wei
Chng, Wee Joo
Tay, Chor Yong
McCarthy, Neil E.
Lim, Sai Kiang
Sze, Siu Kwan
Keywords: Science::Biological sciences
Issue Date: 2020
Source: Tse, S. W., Tan, C. F., Park, J. E., Gnanasekaran, J., Gupta, N., Low, J. K., . . . Sze, S. K. (2020). Microenvironmental hypoxia induces dynamic changes in lung cancer synthesis and secretion of extracellular vesicles. Cancers, 12(10), 2917-. doi:10.3390/cancers12102917
Project: MOE2016-T2-2-018
Journal: Cancers
Abstract: Extracellular vesicles (EVs) mediate critical intercellular communication within healthy tissues, but are also exploited by tumour cells to promote angiogenesis, metastasis, and host immunosuppression under hypoxic stress. We hypothesize that hypoxic tumours synthesize hypoxia-sensitive proteins for packing into EVs to modulate their microenvironment for cancer progression. In the current report, we employed a heavy isotope pulse/trace quantitative proteomic approach to study hypoxia sensitive proteins in tumour-derived EVs protein. The results revealed that hypoxia stimulated cells to synthesize EVs proteins involved in enhancing tumour cell proliferation (NRSN2, WISP2, SPRX1, LCK), metastasis (GOLM1, STC1, MGAT5B), stemness (STC1, TMEM59), angiogenesis (ANGPTL4), and suppressing host immunity (CD70). In addition, functional clustering analyses revealed that tumour hypoxia was strongly associated with rapid synthesis and EV loading of lysosome-related hydrolases and membrane-trafficking proteins to enhance EVs secretion. Moreover, lung cancer-derived EVs were also enriched in signalling molecules capable of inducing epithelial-mesenchymal transition in recipient cancer cells to promote their migration and invasion. Together, these data indicate that lung-cancer-derived EVs can act as paracrine/autocrine mediators of tumorigenesis and metastasis in hypoxic microenvironments. Tumour EVs may, therefore, offer novel opportunities for useful biomarkers discovery and therapeutic targeting of different cancer types and at different stages according to microenvironmental conditions.
ISSN: 2072-6694
DOI: 10.3390/cancers12102917
Rights: © 2020 The Authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (
Fulltext Permission: open
Fulltext Availability: With Fulltext
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