Dolores Di Vizio,
Professor,
Cedars Sinai Medical Center
Dr. Dolores Di Vizio is a pathologist and a molecular and cell biologist trained at Albert Einstein College of Medicine, and Harvard Medical School. Dr. Di Vizio holds an academic appointment as associate professor at Cedars-Sinai Medical Center, and at the University of California, Los Angeles. She is an Executive Chair of the International Society of Extracellular Vesicles (ISEV). Her group studies the molecular mechanisms of progression to advanced disease in human tumors, with a particular emphasis on large oncosomes, extracellular vesicles (EVs) shed into the extracellular space from fast migrating and metastatic amoeboid cancer cells. Her lab is currently profiling the large oncosomes and other EV populations by NGS and proteomics for functional and molecular characterization.
Large Oncosomes and Other Extracellular Vesicles: A Source of Cancer-derived Circulating Markers
Tuesday, 28 October 2014 at 14:45
Add to Calendar ▼2014-10-28 14:45:002014-10-28 15:45:00Europe/LondonLarge Oncosomes and Other Extracellular Vesicles: A Source of Cancer-derived Circulating MarkersSELECTBIOenquiries@selectbiosciences.com
We recently discovered that rapidly migratory, “amoeboid” prostate cancer cells shed large (1-10µm diameter), bioactive extracellular vesicles (EVs), termed large oncosomes. Large oncosomes can be selectively isolated by differential centrifugation and/or by filtration, and analyzed by immuno-flow cytometry with specific size beads in vitro and in vivo. Their quantitation in the circulation reports metastatic disease in patients and animal models (Cancer Res. 2009; Am J Pathol. 2012). In order to profile large oncosomes at a molecular level, we performed next generation sequencing (whole genome and RNA-seq) and quantitative proteomics studies (LC-MS/MS SILAC). We demonstrated the feasibility of RNA-seq analysis of EVs purified from human platelet-poor plasma and have obtained a minimum of 50 million paired end reads per sample. After mapping to RefSeq-annotated human gene loci and quantification as FPKM (fragments per kilobase of exon per million fragments mapped), a number of transcripts were identified as differentially expressed between patients with breast cancer and normal subjects (FDR <0.05). We also performed whole genome paired-end sequencing (Illumina) of large oncosome-derived DNA and demonstrated that single nucleotide mutations, insertions/deletions, and translocations present in donor cells can be identified in large oncosomes. Finally, SILAC profiling of tumor cell-derived large oncosomes in comparison with smaller EVs including exosomes demonstrated enrichment, in large oncosomes, of proteins functionally involved in cell cycle regulation, anti-apoptosis, and cell motility. Among the classes of proteins often identified in EVs, a cohort of these “exosome” biomarkers were significantly enriched in large oncosomes. These findings identify large oncosomes as a novel class of EV that contains clinically relevant biomarkers.
Add to Calendar ▼2014-10-27 00:00:002014-10-28 00:00:00Europe/LondonBiofluid BiopsiesSELECTBIOenquiries@selectbiosciences.com
Add to Calendar ▼2014-10-28 14:45:002014-10-28 15:45:00Europe/LondonLarge Oncosomes and Other Extracellular Vesicles: A Source of Cancer-derived Circulating MarkersSELECTBIOenquiries@selectbiosciences.com
