TY - JOUR
T1 - Extracellular vesicles carry distinct proteo-transcriptomic signatures that are different from their cancer cell of origin
AU - Chen, Tzu Yi
AU - Gonzalez-Kozlova, Edgar
AU - Soleymani, Taliah
AU - La Salvia, Sabrina
AU - Kyprianou, Natasha
AU - Sahoo, Susmita
AU - Tewari, Ashutosh K.
AU - Cordon-Cardo, Carlos
AU - Stolovitzky, Gustavo
AU - Dogra, Navneet
N1 - Funding Information:
The authors thank Drs. Sung-Cheol Kim, Benjamin H. Wunsch, Stacey M. Gifford, Joshua T. Smith, Huan Hu, and Pablo Meyer for help with nanoDLD chip technology. Drs. Kamlesh K. Yadav, Sujit Nair, Rachel Weil, Kamala Bhatt for help with patient sample collection. Drs. Anoop Pal (izon), Pragnesh Patel (izon). The authors thank Drs. Veronica Sanchez-Gonzalez and George Daaboul (NanoView Biosciences, Boston, MA) for helping with the Exoview analysis. Kimaada Allette, Melissa Smith, Adam Margolin, Bojan Losic, Robert P. Sebra for help with genomic sequencing and analyses. Drs. Manuel Meyer and Emily Chen for help with mass spectrometry. Dr. Ronald E. Gordon for help with electron microscopy. The authors thank the office of Scientific Computing and the Genomics Core Facility at the Icahn School of Medicine at Mount Sinai (ISMMS) for providing computational resources and staff expertise, as well as the ISMMS Biorepository for providing some of the samples. The authors thank following funding agencies and foundations: International Business Machine (IBM) (ND, GS); National Institutes of Health NHLBI, R01HL148786 (ND, SL, SS); The Alzheimer's Disease Research Center & Friedman Brain Institute at Mount Sinai (ND); R01CA232574/National Institutes of Health/NCI (NK), the Deane Prostate Health and The Arthur M. Blank Family Foundation (AKT). Conceptualization: ND and GS. Writing - original draft preparation: ND, TC, and EGK. Writing - review & editing: TC, EGK, TS, SL, NK, SS, AKT, CCC, GS, and ND. Data curation: TC, EGK, TS, AKT, CCC, GS, and ND. Visualization: TC, EGK, TS, and ND. Supervision: ND. Funding acquisition: ND, GS, AKT, and CCC. All authors have read and agreed to the published version of the manuscript. The authors declare no competing interests.
Publisher Copyright:
© 2022 The Authors
PY - 2022/6/17
Y1 - 2022/6/17
N2 - Circulating extracellular vesicles (EVs) contain molecular footprints—lipids, proteins, RNA, and DNA—from their cell of origin. Consequently, EV-associated RNA and proteins have gained widespread interest as liquid-biopsy biomarkers. Yet, an integrative proteo-transcriptomic landscape of EVs and comparison with their cell of origin remains obscure. Here, we report that EVs enrich distinct proteo-transcriptome that does not linearly correlate with their cell of origin. We show that EVs enrich endosomal and extracellular proteins, small RNA (∼13–200 nucleotides) associated with cell differentiation, development, and Wnt signaling. EVs cargo specific RNAs (RNY3, vtRNA, and MIRLET-7) and their complementary proteins (YBX1, IGF2BP2, and SRSF1/2). To ensure an unbiased and independent analyses, we studied 12 cancer cell lines, matching EVs (inhouse and exRNA database), and serum EVs of patients with prostate cancer. Together, we show that EV-RNA-protein complexes may constitute a functional interaction network to protect and regulate molecular access until a function is achieved.
AB - Circulating extracellular vesicles (EVs) contain molecular footprints—lipids, proteins, RNA, and DNA—from their cell of origin. Consequently, EV-associated RNA and proteins have gained widespread interest as liquid-biopsy biomarkers. Yet, an integrative proteo-transcriptomic landscape of EVs and comparison with their cell of origin remains obscure. Here, we report that EVs enrich distinct proteo-transcriptome that does not linearly correlate with their cell of origin. We show that EVs enrich endosomal and extracellular proteins, small RNA (∼13–200 nucleotides) associated with cell differentiation, development, and Wnt signaling. EVs cargo specific RNAs (RNY3, vtRNA, and MIRLET-7) and their complementary proteins (YBX1, IGF2BP2, and SRSF1/2). To ensure an unbiased and independent analyses, we studied 12 cancer cell lines, matching EVs (inhouse and exRNA database), and serum EVs of patients with prostate cancer. Together, we show that EV-RNA-protein complexes may constitute a functional interaction network to protect and regulate molecular access until a function is achieved.
KW - Cancer systems biology
KW - Microenvironment
KW - Transcriptomics
UR - http://www.scopus.com/inward/record.url?scp=85131051484&partnerID=8YFLogxK
U2 - 10.1016/j.isci.2022.104414
DO - 10.1016/j.isci.2022.104414
M3 - Article
AN - SCOPUS:85131051484
SN - 2589-0042
VL - 25
JO - iScience
JF - iScience
IS - 6
M1 - 104414
ER -