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https://doi.org/10.3390/cancers12102917
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 & Technology Life Sciences & Biomedicine Oncology extracellular vesicles hypoxia tumour microenvironment epithelial– mesenchymal transition tumorigenesis pulsed-SILAC quantitative proteomics EPITHELIAL-MESENCHYMAL TRANSITION INDUCIBLE FACTOR HEPATOCELLULAR-CARCINOMA COLORECTAL-CANCER SIGNALING PATHWAY CELL-ADHESION METASTASIS GROWTH INVASION PROMOTES |
Issue Date: | 1-Oct-2020 | Publisher: | MDPI | Citation: | 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 (2020-10-01). Microenvironmental Hypoxia Induces Dynamic Changes in Lung Cancer Synthesis and Secretion of Extracellular Vesicles. CANCERS 12 (10). ScholarBank@NUS Repository. https://doi.org/10.3390/cancers12102917 | 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. | Source Title: | CANCERS | URI: | https://scholarbank.nus.edu.sg/handle/10635/229001 | ISSN: | 20726694 | DOI: | 10.3390/cancers12102917 |
Appears in Collections: | Staff Publications Elements |
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