When doctors detect elevated levels of SerpinB3 in a blood test, it can
signal that something is seriously wrong, from hard-to-treat cancers to severe
inflammatory conditions.
SerpinB3 is a critical protein that often reveals when the body's barrier
tissues, like the skin or lungs, are under serious stress from cancer or
chronic illness.
But new research from Arizona State University shows that SerpinB3, long
recognized as a disease marker, also has a natural role in the body: helping to
heal wounds.
Skin wounds remain a major challenge for medicine. Of the roughly 6 million
wounds that occur annually in the U.S., many are difficult to treat and are
often linked to diabetes, burns, infection or advanced age. Together, these
hard-to-heal wounds cost an estimated $20 billion each year.
In a new study, co-authors Jordan Yaron, Kaushal
Rege and their colleagues with the Biodesign Center for Biomaterials Innovation
and Translation discovered that SerpinB3 is part of the body's natural
wound-healing arsenal, helping the skin recover after damage.
The research points to new possibilities: Boosting it could improve wound
healing, while blocking it may offer a way to fight aggressive cancers. The
findings may also help explain SerpinB3's role in inflammatory ailments, from
skin conditions to asthma.
The research appears in Proceedings of the National Academy of
Sciences.
The study grew out of a convergence of the team's broader work on bioactive materials for
wound repair and expertise studying a family of proteins called serpins—short
for serine protease inhibitors. Serpins act as important regulators of diverse
processes such as blood clotting and immune regulation throughout the body, with
several serpins having apparent roles in keeping tissue breakdown and repair in
balance.
"When we looked deeper into how our bioactive nanomaterials were
helping tissue repair, SerpinB3, a protein originally implicated in cancer,
jumped at us as a key factor that correlated with nanomaterial-driven wound healing," Rege said. "This journey, which started
from use-inspired research on biomaterials for tissue repair to uncovering the
fundamental role of this protein as an injury-response mechanism in skin, has
been truly fascinating. We are now building on this basic finding and
investigating the role of SerpinB3 in other pathological conditions."
Rege is a professor of chemical engineering and director of the Biodesign
Center for Biomaterials Innovation and Translation. Yaron is an assistant
professor of chemical engineering and faculty with the center. Both
investigators hold academic appointments with the School for Engineering of
Matter, Transport and Energy at ASU.
SerpinB3's split identity
Many serpins are linked with disease when their balance in the body goes
awry, showing up in inflammation, fibrosis and cancer. One member of this
family, SerpinB3, has been used extensively in cancer tests as an indicator of
aggressive disease.
SerpinB3—also known as squamous cell carcinoma antigen-1—was first
discovered in cervical cancer tissue in 1977. It has long been applied as a
biomarker of aggressive cancers in the lung, liver and skin, where high levels
are tied to poor outcomes.
"For more than four decades, SerpinB3 has been recognized as a driver
of cancer growth and metastasis—so much so that it became a clinical
diagnostic. Yet after all this time, its normal role in the body remained a
mystery," Yaron said. "But when we looked at injured, healing skin,
we found that cells moving into the wound bed were producing enormous amounts
of this protein. It became clear that this is part of the machinery humans
evolved to heal epithelial injuries, a process that cancer cells have learned
to exploit to spread. This now opens the doors to understanding how this
protein is involved in many more diseases."
How SerpinB3 helps wounds close
By tracking which genes switch on during healing, the researchers found
that SerpinB3 levels surged in wounded skin. The increase was especially strong
in wounds covered with advanced biomaterial dressings, a finding
built on the group's earlier research, showing how such materials can boost the
body's natural repair signals.
In lab tests, adding extra SerpinB3 made skin cells move and cover wounds
faster, working as effectively as a well-known healing booster called Epidermal
Growth Factor. SerpinB3 works by activating keratinocytes—the skin cells that
normally move in to repair damage. When switched on, these cells become less
sticky and more mobile, allowing them to slide into the wound and rebuild
tissue.
The protein also assists the body's natural repair networks, guiding
healing and new tissue growth. Treated wounds showed more neatly arranged collagen fibers, which act as a support structure, helping restore
the skin's strength and integrity.
Implications for care
The researchers note that more work is needed to understand how SerpinB3
fits into the body's broader systems of healing. Because SerpinB3 speeds up
repair, it could one day be developed as a treatment for stubborn wounds—like
pressure sores and other ulcers that heal slowly over time.
By revealing SerpinB3's double life, the study shows how a deeper understanding of the body's own repair systems could lead to better treatments for wounds—and new strategies to fight cancer.
Source: Protein linked to cancer found to play key role in wound healing
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