Nav: Home

Shedding light on cancer metabolism in real-time with bioluminescence

May 20, 2019

EPFL scientists have invented a new way to quantify - in real-time - glucose metabolism of cancerous tumors by making them bioluminesce. This new light probe is not radioactive and works on living organisms such as mice that carry the tumor cells. The technique requires tagged tumor cells, two jabs and a camera. The results are published in Nature Methods.

Take a mouse with a tumor tagged with luciferase. Luciferase-expressing tumors are made by taking a sample of the cancerous tumor from a patient, and chemically labeling them with luciferase, a class of oxidative enzymes that produce bioluminescence. These labeled cells are grown in mice to understand the basic biology of the cancer and for the development of effective cancer treatments.

Next, inject a first compound in the mouse that doesn't easily break down in the blood. Twenty-four hours later, inject a second compound that is designed to react only with the first under very specific conditions.

The reaction between the two compounds is engineered to produce bioluminescent light which escapes the body, like in fireflies, but happens where luciferase-expressing tumors have metabolized sugar. Point a CCD camera sensor at the body and you have a snapshot of the tumor's metabolic levels. The amount of light produced is directly proportional to the amount of metabolized sugar.

"We wanted to develop a tool to help create more effective cancer treatments," explains EPFL chemist Elena Goun of Laboratory of Bioorganic Chemistry and Molecular Imaging who led the study. "Our new imaging technique allows us to quantify how much sugar is being metabolized in real-time, providing valuable information about the metabolic status of the tumor and the types of drugs that could deprive the tumor of its major energy source."

How it works: from fireflies to cancer imaging

Goun and her team found inspiration from the way fireflies glow and combined it with click-chemistry, a branch of chemical biology in which biocompatible molecules are designed to specifically "click" together in a tailored reaction that happens directly in the complex environment of the living organism.

Since cancer has a high metabolic rate, it consumes sugar in large amounts. This process is important for cancer growth and metastasis but remains poorly understood due to the lack of non-invasive tools that work at the level of the entire organism.

Goun's idea was to engineer two click-molecules, one with sugar and the other with the "caged" luciferin, the light-emitting compound found in fireflies that make them glow. And it works.

Once the click-labeled sugar is eaten by the tumor, it reacts with this "caged" luciferin via the "click" reaction and produces bioluminescent light proportional to the amount of sugar entering the cells. She termed her firefly imaging technique BiGluc, short for "Bioluminescent glucose".

BiGluc could be used to understand the metabolic requirements of different tumors, opening avenues for the generation of novel, effective treatments.

BiGluc in preclinical imaging of cancer metabolism and drug development

"Our novel optical imaging technique has high clinical applicability and many advantages," says Goun. "It is non-radioactive, highly sensitive and quantifiable, the reagents are stable for years, and the glow can be observed for many hours."

Due to its versatile nature, BiGluc could also be extended beyond cancer to image dysfunctional cells of many other important human pathologies in which changes in metabolism play a key role, such as diabetes, neurodegenerative diseases, nonalcoholic steatohepatitis, and many others.

"What's exciting about these results is that we have created the foundation for the development of an ultra-sensitive imaging platform for quantifying the uptake of many important metabolites that play a central role in multiple human diseases with the goal of creating more effective treatments," says Goun.
-end-


Ecole Polytechnique Fédérale de Lausanne

Related Cancer Articles:

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.
Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.
Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.
Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.
More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.
New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.
American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.
Oncotarget: Cancer pioneer employs physics to approach cancer in last research article
In the cover article of Tuesday's issue of Oncotarget, James Frost, MD, PhD, Kenneth Pienta, MD, and the late Donald Coffey, Ph.D., use a theory of physical and biophysical symmetry to derive a new conceptualization of cancer.
Health indicators for newborns of breast cancer survivors may vary by cancer type
In a study published in the International Journal of Cancer, researchers from the UNC Lineberger Comprehensive Cancer Center analyzed health indicators for children born to young breast cancer survivors in North Carolina.
Few women with history of breast cancer and ovarian cancer take a recommended genetic test
More than 80 percent of women living with a history of breast or ovarian cancer at high-risk of having a gene mutation have never taken the test that can detect it.
More Cancer News and Cancer Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Teaching For Better Humans 2.0
More than test scores or good grades–what do kids need for the future? This hour, TED speakers explore how to help children grow into better humans, both during and after this time of crisis. Guests include educators Richard Culatta and Liz Kleinrock, psychologist Thomas Curran, and writer Jacqueline Woodson.
Now Playing: Science for the People

#556 The Power of Friendship
It's 2020 and times are tough. Maybe some of us are learning about social distancing the hard way. Maybe we just are all a little anxious. No matter what, we could probably use a friend. But what is a friend, exactly? And why do we need them so much? This week host Bethany Brookshire speaks with Lydia Denworth, author of the new book "Friendship: The Evolution, Biology, and Extraordinary Power of Life's Fundamental Bond". This episode is hosted by Bethany Brookshire, science writer from Science News.
Now Playing: Radiolab

Space
One of the most consistent questions we get at the show is from parents who want to know which episodes are kid-friendly and which aren't. So today, we're releasing a separate feed, Radiolab for Kids. To kick it off, we're rerunning an all-time favorite episode: Space. In the 60's, space exploration was an American obsession. This hour, we chart the path from romance to increasing cynicism. We begin with Ann Druyan, widow of Carl Sagan, with a story about the Voyager expedition, true love, and a golden record that travels through space. And astrophysicist Neil de Grasse Tyson explains the Coepernican Principle, and just how insignificant we are. Support Radiolab today at Radiolab.org/donate.