'Supermeres' may carry clues to cancer, Alzheimer's disease and COVID-19


Date:
December 13, 2021
Source:
Vanderbilt University Medical Center
Summary:
Researchers have discovered a nanoparticle released from cells,
called a 'supermere,' which contains enzymes, proteins and
RNA associated with multiple cancers, cardiovascular disease,
Alzheimer's disease and even COVID-19.



FULL STORY ========================================================================== Researchers at Vanderbilt University Medical Center have discovered a nanoparticle released from cells, called a "supermere," which contains
enzymes, proteins and RNA associated with multiple cancers, cardiovascular disease, Alzheimer's disease and even COVID-19.


==========================================================================
The discovery, reported in Nature Cell Biology, is a significant advance
in understanding the role extracellular vesicles and nanoparticles play
in shuttling important chemical "messages" between cells, both in health
and disease.

"We've identified a number of biomarkers and therapeutic targets in
cancer and potentially in a number of other disease states that are
cargo in these supermeres," said the paper's senior author, Robert
Coffey, MD. "What is left to do now is to figure out how these things get released." Coffey, the Ingram Professor of Cancer Research and professor
of Medicine and Cell & Developmental Biology, is internationally known for
his studies of colorectal cancer. His team is currently exploring whether
the detection and targeting of cancer-specific nanoparticles in the
bloodstream could lead to earlier diagnoses and more effective treatment.

In 2019 Dennis Jeppesen, PhD, a former research fellow in Coffey's lab
who is now a research instructor in Medicine, used advanced techniques to isolate and analyze small membrane-enclosed extracellular vesicles called "exosomes." That year, using high-speed ultracentrifugation, another
of Coffey's colleagues, Qin Zhang, PhD, research assistant professor of Medicine, devised a simple method to isolate a nanoparticle called an
"exomere" that lacks a surface coat.



==========================================================================
In the current study, Zhang took the "supernatant," or fluid that remains
after the exomeres have been spun into a "pellet," and spun the fluid
faster and longer.

The result was a pellet of nanoparticles isolated from the supernatant
of the exomere spin -- which the researchers named supermeres. "They're
also super- interesting," Coffey quipped, "because they contain many
cargo previously thought to be in exosomes." For one thing, supermeres
carry most of the extracellular RNA released by cells and which is found
in the bloodstream. Among other functional properties, cancer-derived supermeres can "transfer" drug resistance to tumor cells, perhaps via
the RNA cargo they deliver, the researchers reported.

Supermeres are important carriers of TGFBI, a protein that in established tumors promotes tumor progression. TGFBI thus may be a useful marker
in liquid biopsies for patients with colorectal cancer, the researchers
noted.

They also carry ACE2, a cell-surface receptor that plays a role in cardiovascular disease and is the target of the COVID-19 virus. This
raises the possibility that ACE2 carried by supermeres could serve as a
"decoy" to bind the virus and prevent infection.



========================================================================== Another potentially important cargo is APP, the amyloid-beta precursor
protein implicated in the development of Alzheimer's disease. Supermeres
can cross the blood-brain barrier, suggesting that their analysis
could improve early diagnosis or possibly even targeted treatment of
the disease.

"The identification of this rich plethora of bioactive molecules
... raises interesting questions about the function of supermeres, and heightens interest in the potential of these particles as biomarkers
for diseases," researchers at the University of Notre Dame noted in a
review published with the paper.

Zhang, Jeppesen and James Higginbotham, PhD, research instructor in
Medicine, are the paper's first authors.

Other VUMC co-authors: Ramona Graves-Deal, Vincent Q. Trinh, MD, Marisol Ramirez, MS, Yoojin Sohn, Abigail Neininger, Nilay Taneja, PhD, Eliot
McKinley, PhD, Hiroaki Niitsu, MD, PhD, Zheng Cao, MD, PhD, Rachel
Evans, Sarah E. Glass, Kevin Ray, William Fissell, MD, Salisha Hill,
MS, Kristie Rose, PhD, Mary Kay Washington, MD, PhD, Gregory Ayers,
MS, Dylan Burnette, PhD, Jeffrey Franklin, PhD, Youngmin Lee, MD, PhD,
and Qi Liu, PhD.

Research support included National Institutes of Health grants GM125028, CA218386, CA211015, CA197570, CA236733, CA241685 and CA229123,
the Nicholas Tierney GI Cancer Memorial Fund, and an American Heart
Association Postdoctoral Fellowship.

========================================================================== Story Source: Materials provided by
Vanderbilt_University_Medical_Center. Original written by Bill
Snyder. Note: Content may be edited for style and length.


========================================================================== Journal References:
1. Qin Zhang, Dennis K. Jeppesen, James N. Higginbotham, Ramona
Graves-Deal,
Vincent Q. Trinh, Marisol A. Ramirez, Yoojin Sohn, Abigail
C. Neininger, Nilay Taneja, Eliot T. McKinley, Hiroaki Niitsu,
Zheng Cao, Rachel Evans, Sarah E. Glass, Kevin C. Ray, William
H. Fissell, Salisha Hill, Kristie Lindsey Rose, Won Jae Huh, Mary
Kay Washington, Gregory Daniel Ayers, Dylan T. Burnette, Shivani
Sharma, Leonard H. Rome, Jeffrey L. Franklin, Youngmin A. Lee,
Qi Liu, Robert J. Coffey. Supermeres are functional extracellular
nanoparticles replete with disease biomarkers and therapeutic
targets. Nature Cell Biology, 2021; DOI: 10.1038/s41556-021- 00805-8
2. James W. Clancy, Alex C. Boomgarden, Crislyn
D'Souza-Schorey. Profiling
and promise of supermeres. Nature Cell Biology, 2021; DOI: 10.1038/
s41556-021-00808-5 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/12/211213121854.htm

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