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During the coronavirus shutdown, we are tracking online seminars and classes related to exRNA and EV research.

This blog originated as a press release from Cedars-Sinai. Thanks to them for allowing us to repost it here.

Analysis of particles shed by tumors points to new, less invasive way to diagnose malignancies

A recent study sheds light on proteins in particles called extracellular vesicles, which are released by tumor cells into the bloodstream and promote the spread of cancer. The findings suggest how a blood test involving these vesicles might be used to diagnose cancer in the future, avoiding the need for invasive surgical biopsies.

Extracellular vesicles Extracellular vesicles
Credit: NIH

The research is a large-scale analysis of what are known as palmitoylated proteins inside extracellular vesicles, according to Dolores Di Vizio, MD, PhD, professor of Surgery, Biomedical Sciences and Pathology and Laboratory Medicine at Cedars-Sinai. Di Vizio is co-corresponding author of the study, published online June 10 in the Journal of Extracellular Vesicles.

Extracellular vesicles have gained significant attention in the last decade because they contain proteins and other biologically important molecules whose information can be transferred from cell to cell. They are known to help cancer metastasize to distant sites in the body, but exactly how this happens is not clear.

To learn more about this process, the research team looked into a process called palmitoylation, in which enzymes transfer lipid molecules onto proteins. Palmitoylation can affect where proteins are located within cells, their activities, and their contribution to cancer progression.

The investigators examined two types of extracellular vesicles, small and large, in samples of human prostate cancer cells. Using centrifuges, they separated the extracellular vesicles from the other cell materials and analyzed the levels of palmitoylation and the types of proteins present.

The team found extracellular vesicles derived from the cancer cells contained palmitoylated proteins that are associated with the spread of cancer. Further, when the team chemically suppressed the palmitoylation process, the level of some of these proteins went down in the extracellular vesicles.

“Our results suggest that protein palmitoylation may be involved in the selective packaging of proteins to different extracellular vesicle populations in the body,” Di Vizio said. “This finding raises the possibility that by examining these proteins in extracellular vesicles in the bloodstream, we may be able to detect and characterize cancer in a patient in the future without performing a surgical biopsy.”

Dolores Di Vizio Dolores Di Vizio, MD, PhD
Professor of Surgery, Biomedical Sciences and Pathology
and Laboratory Medicine at Cedars-Sinai.

Di Vizio said the next step in the research is to conduct a study in collaboration with her Cedars-Sinai colleagues and industry partners that will use advanced technologies, including mass spectrometry and flow cytometry, with the goal of identifying clinically significant prostate cancer at diagnosis.

In addition to Di Vizio, Wei Yang, PhD, associate professor of Surgery at Cedars-Sinai, and Andries Zijlstra, PhD, are co-corresponding authors for the study. Zijlstra completed the research while working at Vanderbilt University Medical Center in Nashville. Javier Mariscal, PhD, a postdoctoral scientist in Di Vizio’s laboratory, is the study’s first author.

Reference
Mariscal J et al. Comprehensive palmitoyl-proteomic analysis identifies distinct protein signatures for large and small cancer-derived extracellular vesicles. (2020) J Extracell Vesicles 9:1764192. doi: 10.1080/20013078.2020.1764192. PMID: 32944167.

Funding: Research reported in this publication was supported by the National Institutes of Health under award number R01CA218526 and by the U.S. Department of Defense.

This blog originated as a press release from the University of Sussex. Thanks to them for allowing us to repost it here.

Scientists at the University of Sussex have identified a potential pattern within blood which signals the presence of motor neuron disease; a discovery which could significantly improve diagnosis.

Currently, it can take up to a year for a patient to be diagnosed with amyotrophic lateral sclerosis (ALS), more commonly known as motor neuron disease (MND).

But after comparing blood samples from patients with ALS, those with other motor-related neurological diseases, and healthy patients, researchers were able to identify specific biomarkers which act as a diagnostic signature for the disease.

Researchers hope that their findings, published in the journal Brain Communications, and funded by the Motor Neurone Disease Association (MNDA), could lead to the development of a blood test which will identify the unique biomarker, significantly simplifying and speeding up diagnosis.

With patients living, on average, just 2-5 years after diagnosis, this time could be crucial.

Professor Majid Hafezparast, a professor of Molecular Neuroscience at the University of Sussex, led the research in collaboration with Professors Nigel Leigh and Sarah Newbury from the Brighton and Sussex Medical School, Martin Turner from the University of Oxford, Andrea Malaspina from Queen Mary, University of London, and Albert Ludolph from the University of Ulm.

He said: “In order to effectively diagnose and treat ALS, we are in urgent need of biomarkers as a tool for early diagnosis and for monitoring the efficacy of therapeutic interventions in clinical trials.

“Biomarkers can indicate the disease is present and help us to predict its progression rate.

“In our study, we compared serum samples taken from the blood of 245 patients and controls, analysing their patterns of non-coding ribonucleic acids (ncRNA).

“We found a biomarker signature for motor neurone disease that is made up of a combination of seven ncRNAs. When these ncRNA are expressed in a particular pattern, we are able to classify whether our samples come from ALS patients or controls.”

Biomarker discovery pipeline

Dr Greig Joilin, the research fellow who undertook this work in Professor Hafezparast’s team said: “We hope that, with further work to validate these biomarkers, a blood test could be developed to help improve diagnosis of motor neuron disease.

“We are now looking to see whether they can predict prognosis to give patients and their families some insight as they begin to understand the disease. Our work could also help other scientists to measure the effectiveness of potential drug treatments against the ncRNA levels. Further, it provides new insight into the cellular and molecular events that contribute to the disease.”

ALS is a group of conditions which affects the nerves in the brain and spinal cord leading to weakness in the muscles and rapid deterioration.

Doctors still don’t know why this happens and there is currently no cure, although existing drug treatments can help patients with daily life and extend life expectancy – but only by two to four months on average.

Stephen Hawking is perhaps one of the most famous cases of motor neuron disease, but more recently Geoff Whaley and his wife Ann brought to light the troubling situation of patients in the UK who wish to end their life before the final phase of the disease takes hold.

Professor Hafezparast hopes that his team’s discovery will improve the outlook for patients by improving diagnosis and giving other researchers a valuable tool to test potential treatments. The researchers are now looking to validate this biomarker signature in a larger cohort of patients and begin to understand why these ncRNAs change in ALS patients.

Reference
Joilin G, et al. Identification of a potential non-coding RNA biomarker signature for Amyotrophic Lateral Sclerosis. (2020) Brain Commun. 2: fcaa053. doi: 110.1093/braincomms/fcaa053 PMID: 32613197.

This blog originated as a press release from ISGlobal, the Barcelona Institute for Global Health. Thanks to ISGlobal for permission to post it here.

A new study shows that extracellular vesicles from the malaria parasite Plasmodium vivax promote parasite adhesion to spleen cells

Extracellular vesicles (EVs) play a role in the pathogenesis of malaria vivax, according to a study led by researchers from the Barcelona Institute for Global Health (ISGlobal), an institution supported by the ”la Caixa” Foundation, and the Germans Trias i Pujol Research Institute (IGTP). The findings, published in Nature Communications, indicate that EVs from P. vivax patients communicate with spleen fibroblasts promoting the adhesion of parasite-infected red blood cells. These data provide important insights into the pathology of vivax malaria. The study was carried out at the Can Ruti Campus, with the participation of the IGTP Genomics platform, the Nephrology service of the Germans Trias i Pujos Hospital, and researchers from the Irsicaixa AIDS Research Institute.

Plasmodium vivax is the most widely distributed human malaria parasite, mostly outside sub-Saharan Africa, and responsible for millions of clinical cases yearly, including severe disease and death. The mechanisms by which P. vivax causes disease are not well understood. Recent evidence suggests that, similar to what has been observed with the more lethal P. falciparum, red blood cells infected by the parasite may accumulate in internal organs and that this could contribute to the pathology of the disease. In fact, the team led by Hernando A. del Portillo and Carmen Fernández-Becerra, recently showed that P. vivax-infected red blood cells adhere to human spleen fibroblasts thanks to the surface expression of certain parasite proteins, and that this expression is induced by the spleen itself. “These findings indicate that the spleen plays a dual role in malaria vivax,” says ICREA researcher Hernando A del Portillo. “On one hand, it eliminates infected red blood cells. On the other hand, it may serve as a “hiding” place for the parasite.” This could explain why P. vivax can cause severe disease in spite of low peripheral blood parasitemia.

Hernando A. del Portillo and Carmen Fernández-Becerra
Hernando A. del Portillo and Carmen Fernández-Becerra

To understand the molecular mechanisms responsible for this adhesion process, the research team turned its attention to something they have been working on for the last few years: extracellular vesicles. These small particles surrounded by a membrane are naturally released from almost any cell and play a role in communication between cells. There is increasing evidence that they could be involved in a wide range of pathologies, including parasitic diseases such as malaria. “Our new findings reveal, for what we believe is the first time, a physiological role of EVs in malaria,” says del Portillo, last author of the study.

The research team isolated EVs from the blood of patients with acute P. vivax infection or from healthy volunteers and showed a very efficient uptake of the former by human spleen fibroblasts. Furthermore, this uptake induced the expression of a molecule (ICAM-1) on the surface of the fibroblast which in turn serves as an “anchor” for the adherence of P. vivax-infected red blood cells.

“Our study provides insight into the role of extracellular vesicles in malaria vivax and supports the existence of parasite populations adhering to particular cells of the spleen, where they can multiply while not circulating in the blood” says Fernández-Becerra, senior co-author of the study. “Importantly, these hidden infections could represent an additional challenge to disease diagnosis and elimination efforts as they might be the source of asymptomatic infections,” she adds.

Reference
Toda H, Diaz-Varela M, Segui-Barber J. Plasma-derived extracellular vesicles from Plasmodium vivax patients signal spleen fibroblasts via NF-kB facilitating parasite cytoadherence. Nat Commun 11:2761. doi: 10.1038/s41467-020-16337-y PMID: 32487994.