Distinct mRNAs in Cancer Extracellular Vesicles Activate Angiogenesis and Alter Transcriptome of Vascular Endothelial Cells
Cancer-derived extracellular vesicles (EVs) have been demonstrated to be implicated in various processes of cancer development, with most of the EV-induced changes attributed to EV-proteins and EV-microRNAs. However, the knowledge about the abundance of cancer EV-mRNAs and their contribution to canc...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-04-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/9/2009 |
| _version_ | 1797536789418737664 |
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| author | Pan Zhang Su Bin Lim Kuan Jiang Ti Weng Chew Boon Chuan Low Chwee Teck Lim |
| author_facet | Pan Zhang Su Bin Lim Kuan Jiang Ti Weng Chew Boon Chuan Low Chwee Teck Lim |
| author_sort | Pan Zhang |
| collection | DOAJ |
| description | Cancer-derived extracellular vesicles (EVs) have been demonstrated to be implicated in various processes of cancer development, with most of the EV-induced changes attributed to EV-proteins and EV-microRNAs. However, the knowledge about the abundance of cancer EV-mRNAs and their contribution to cancer development remain elusive. Here, we show that mRNAs prevail in cancer EVs as compared with normal EVs, and cancer EVs that carry abundant angiogenic mRNAs activate angiogenesis in human umbilical vein endothelial cells (HUVECs). Specifically, of a gene panel comprising 61 hypoxia-targeted oncogenes, a larger proportion is harbored by cancer EVs (>40%) than normal EVs (14.8%). Fluorescent trafficking indicates cancer EVs deliver translatable mRNAs such as <i>VEGFA</i> to HUVECs, contributing to the activation of VEGFR-dependent angiogenesis and the upregulation of epithelial-mesenchymal transition-related and metabolism-related genes. Overall, our findings provide novel insights into EV-mRNAs and their role in angiogenesis, and has potential for diagnostic and therapeutic applications. |
| first_indexed | 2024-03-10T12:05:49Z |
| format | Article |
| id | doaj.art-81ca1f73652448198df068cd6a3a8317 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T12:05:49Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-81ca1f73652448198df068cd6a3a83172023-11-21T16:36:06ZengMDPI AGCancers2072-66942021-04-01139200910.3390/cancers13092009Distinct mRNAs in Cancer Extracellular Vesicles Activate Angiogenesis and Alter Transcriptome of Vascular Endothelial CellsPan Zhang0Su Bin Lim1Kuan Jiang2Ti Weng Chew3Boon Chuan Low4Chwee Teck Lim5NUS Graduate School—Integrative Sciences and Engineering Programme (ISEP), National University of Singapore, Singapore 119077, SingaporeDepartment of Biomedical Engineering, National University of Singapore, Singapore 117583, SingaporeMechanobiology Institute, National University of Singapore, Singapore 117411, SingaporeMechanobiology Institute, National University of Singapore, Singapore 117411, SingaporeNUS Graduate School—Integrative Sciences and Engineering Programme (ISEP), National University of Singapore, Singapore 119077, SingaporeNUS Graduate School—Integrative Sciences and Engineering Programme (ISEP), National University of Singapore, Singapore 119077, SingaporeCancer-derived extracellular vesicles (EVs) have been demonstrated to be implicated in various processes of cancer development, with most of the EV-induced changes attributed to EV-proteins and EV-microRNAs. However, the knowledge about the abundance of cancer EV-mRNAs and their contribution to cancer development remain elusive. Here, we show that mRNAs prevail in cancer EVs as compared with normal EVs, and cancer EVs that carry abundant angiogenic mRNAs activate angiogenesis in human umbilical vein endothelial cells (HUVECs). Specifically, of a gene panel comprising 61 hypoxia-targeted oncogenes, a larger proportion is harbored by cancer EVs (>40%) than normal EVs (14.8%). Fluorescent trafficking indicates cancer EVs deliver translatable mRNAs such as <i>VEGFA</i> to HUVECs, contributing to the activation of VEGFR-dependent angiogenesis and the upregulation of epithelial-mesenchymal transition-related and metabolism-related genes. Overall, our findings provide novel insights into EV-mRNAs and their role in angiogenesis, and has potential for diagnostic and therapeutic applications.https://www.mdpi.com/2072-6694/13/9/2009extracellular vesiclesmessenger RNAcancer biomarkerhypoxiatumor microenvironmentangiogenesis |
| spellingShingle | Pan Zhang Su Bin Lim Kuan Jiang Ti Weng Chew Boon Chuan Low Chwee Teck Lim Distinct mRNAs in Cancer Extracellular Vesicles Activate Angiogenesis and Alter Transcriptome of Vascular Endothelial Cells Cancers extracellular vesicles messenger RNA cancer biomarker hypoxia tumor microenvironment angiogenesis |
| title | Distinct mRNAs in Cancer Extracellular Vesicles Activate Angiogenesis and Alter Transcriptome of Vascular Endothelial Cells |
| title_full | Distinct mRNAs in Cancer Extracellular Vesicles Activate Angiogenesis and Alter Transcriptome of Vascular Endothelial Cells |
| title_fullStr | Distinct mRNAs in Cancer Extracellular Vesicles Activate Angiogenesis and Alter Transcriptome of Vascular Endothelial Cells |
| title_full_unstemmed | Distinct mRNAs in Cancer Extracellular Vesicles Activate Angiogenesis and Alter Transcriptome of Vascular Endothelial Cells |
| title_short | Distinct mRNAs in Cancer Extracellular Vesicles Activate Angiogenesis and Alter Transcriptome of Vascular Endothelial Cells |
| title_sort | distinct mrnas in cancer extracellular vesicles activate angiogenesis and alter transcriptome of vascular endothelial cells |
| topic | extracellular vesicles messenger RNA cancer biomarker hypoxia tumor microenvironment angiogenesis |
| url | https://www.mdpi.com/2072-6694/13/9/2009 |
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