Nav: Home

Linking wound healing and cancer risk

November 26, 2019

When our skin is damaged, a whole set of biological processes springs into action to heal the wound. Now, researchers from the VIB-UGent Center for Inflammation Research have shown that one of the molecules involved in this, HMGB1, slows down wound healing. It is, however, also essential for tumor formation at sites of previous injury. The researchers found that HMGB1 controls the actions of neutrophils, a specific type of immune cells, in skin wounds and that this is crucial for cancer initiation. Targeting this pathway could be beneficial in diabetic wound care and in patients suffering from skin blistering diseases. Their work appears in Cell Reports.

NETting wounds

Wounding initiates a complex repair mechanism that is aimed at fast regeneration of the injured tissue. A large amount of clinical data shows that chronic inflammation or previous injury can predispose tissues to tumor formation, a hypothesis already stated in the nineteenth century.

However, it is still not fully understood what the molecular mechanisms are that link injury repair to cancer. The first immune cells that enter the skin after injury are neutrophils, short-lived immune cells that form specialized structures termed NETs (neutrophil extracellular traps) in skin wounds.

Skin wounds and cancer risk

Dr. Esther Hoste, first author of the study, and colleagues in the group of prof. Geert van Loo (VIB-UGent Center for Inflammation Research) investigated the role of the molecule HMGB1 in injury repair and tumor initiation in the skin. HMGB1 is a molecule that is secreted by damaged tissue and activates the immune system. The scientists genetically deleted HMGB1 from skin cells in mice and showed that their wounds healed faster than normal mice and that they are completely protected from wound-induced tumor formation.

Mice lacking HMGB1 from epithelial skin cells showed reduced neutrophil numbers and NETs in skin wounds. Dr. Hoste explains: "We demonstrated that a mechanism used to alarm your immune system that something is going wrong, can be hijacked for cancer initiation. While secretion of HMGB1 is a good thing in conditions of minor injury, it can be a harmful event in more serious or chronic wounds as it can trigger tumor formation at these wound sites. This really is a case of 'too much of a good thing can hurt you.'"

The harmful NETs that link wound repair to tumor formation were also observed in patients suffering from the severe blistering disease Recessive Dystrophic Epidermolysis Bullosa. These patients undergo repetitive cycles of injury and repair and are at high risk to develop skin cancer.

Faster healing, without cancer

The findings strongly suggest that targeting HMGB1 release or NET formation in the skin might be of interest in blistering diseases or in diabetic patients suffering from chronic ulcers. Such HMGB1-focused therapies could accelerate wound healing responses, while limiting the risk of cancer initiation.

"We were surprised that interfering with the secretion of one molecule provided such benefits to the injury repair process and could completely block tumor formation. We now want to investigate whether this newly identified molecular pathway also affects other tissues where trauma is linked to tumor formation, such as the intestine. We are currently working on new ways to inhibit this detrimental pathway in order to bring our findings to the clinic," says prof. Geert van Loo.

Epithelial HMGB1 delays skin wound healing and drives tumor initiation by priming neutrophils for NET formation, Hoste et al., Cell Reports 2019 DOI number: 10.1016/j.celrep.2019.10.104


FWO Fonds Wetenschappelijk Onderzoek Vlaanderen

Questions from patients

A breakthrough in research is not the same as a breakthrough in medicine. The realizations of VIB researchers can form the basis of new therapies, but the development path still takes years. This can raise a lot of questions. That is why we ask you to please refer questions in your report or article to the email address that VIB makes available for this purpose: Everyone can submit questions concerning this and other medically-oriented research directly to VIB via this address.

VIB (the Flanders Institute for Biotechnology)

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

Listen Again: Meditations on Loneliness
Original broadcast date: April 24, 2020. We're a social species now living in isolation. But loneliness was a problem well before this era of social distancing. This hour, TED speakers explore how we can live and make peace with loneliness. Guests on the show include author and illustrator Jonny Sun, psychologist Susan Pinker, architect Grace Kim, and writer Suleika Jaouad.
Now Playing: Science for the People

#565 The Great Wide Indoors
We're all spending a bit more time indoors this summer than we probably figured. But did you ever stop to think about why the places we live and work as designed the way they are? And how they could be designed better? We're talking with Emily Anthes about her new book "The Great Indoors: The Surprising Science of how Buildings Shape our Behavior, Health and Happiness".
Now Playing: Radiolab

The Third. A TED Talk.
Jad gives a TED talk about his life as a journalist and how Radiolab has evolved over the years. Here's how TED described it:How do you end a story? Host of Radiolab Jad Abumrad tells how his search for an answer led him home to the mountains of Tennessee, where he met an unexpected teacher: Dolly Parton.Jad Nicholas Abumrad is a Lebanese-American radio host, composer and producer. He is the founder of the syndicated public radio program Radiolab, which is broadcast on over 600 radio stations nationwide and is downloaded more than 120 million times a year as a podcast. He also created More Perfect, a podcast that tells the stories behind the Supreme Court's most famous decisions. And most recently, Dolly Parton's America, a nine-episode podcast exploring the life and times of the iconic country music star. Abumrad has received three Peabody Awards and was named a MacArthur Fellow in 2011.