Extracellular vesicles carry distinct proteo-transcriptomic signatures that are different from their cancer cell of origin
Tzu-Yi Chen,
Edgar Gonzalez-Kozlova,
Taliah Soleymani,
Sabrina La Salvia,
Natasha Kyprianou,
Susmita Sahoo,
Ashutosh K. Tewari,
Carlos Cordon-Cardo,
Gustavo Stolovitzky,
Navneet Dogra
Affiliations
Tzu-Yi Chen
Department of Pathology, Icahn School of Medicine at Mount Sinai, New York 10029, USA; Department of Genetics and Genomics Sciences, Icahn School of Medicine at Mount Sinai, New York 10029, USA
Edgar Gonzalez-Kozlova
Department of Genetics and Genomics Sciences, Icahn School of Medicine at Mount Sinai, New York 10029, USA; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Taliah Soleymani
Department of Pathology, Icahn School of Medicine at Mount Sinai, New York 10029, USA; Department of Genetics and Genomics Sciences, Icahn School of Medicine at Mount Sinai, New York 10029, USA
Sabrina La Salvia
Department of Cardiology, Icahn School of Medicine at Mount Sinai, New York 10029, USA
Natasha Kyprianou
Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Urology, Icahn School of Medicine at Mount Sinai, New York 10029, USA
Susmita Sahoo
Department of Cardiology, Icahn School of Medicine at Mount Sinai, New York 10029, USA
Ashutosh K. Tewari
Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Urology, Icahn School of Medicine at Mount Sinai, New York 10029, USA
Carlos Cordon-Cardo
Department of Pathology, Icahn School of Medicine at Mount Sinai, New York 10029, USA; Department of Genetics and Genomics Sciences, Icahn School of Medicine at Mount Sinai, New York 10029, USA; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Gustavo Stolovitzky
Department of Genetics and Genomics Sciences, Icahn School of Medicine at Mount Sinai, New York 10029, USA; IBM T. J. Watson Research Center, Yorktown Heights, New York 10598, USA; Sema4, Stamford, CT 06902, USA
Navneet Dogra
Department of Pathology, Icahn School of Medicine at Mount Sinai, New York 10029, USA; Department of Genetics and Genomics Sciences, Icahn School of Medicine at Mount Sinai, New York 10029, USA; IBM T. J. Watson Research Center, Yorktown Heights, New York 10598, USA; Corresponding author
Summary: 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.
