A protein previously linked to cancer and chronic illnesses has been found to have a natural health benefit.
When doctors find high levels of SerpinB3 in a blood test, it can indicate a serious underlying problem, such as difficult-to-treat cancers or severe inflammatory diseases.
SerpinB3 is an important protein that often appears when the body’s protective tissues, including the skin and lungs, are under significant strain from cancer or chronic illness.
However, researchers at Arizona State University have uncovered a surprising new function for this protein. Beyond its well-known role as a disease indicator, SerpinB3 also plays a natural part in the body’s healing process by aiding in wound repair.
Chronic skin wounds remain a major medical concern. Each year, about 6 million wounds occur in the United States, many of which are slow to heal and connected to conditions such as diabetes, infections, burns or aging. These stubborn wounds collectively cost around $20 billion annually.
In their new study, researchers Jordan Yaron, Kaushal Rege and their team at the Biodesign Center for Biomaterials Innovation and Translation found that SerpinB3 contributes to the body’s own wound-healing mechanisms, helping skin recover after injury.
The discovery opens promising paths for future treatments. Increasing SerpinB3 activity could enhance the body’s ability to heal wounds, while suppressing it might provide new strategies to combat aggressive cancers. The results may also clarify how this protein influences inflammatory disorders, ranging from chronic 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.
Reference: “Squamous cell carcinoma antigen-1/SerpinB3 is an endogenous skin injury response element” by Jordan R. Yaron, Shubham Pallod, Sepideh Nezhadi, Holly M. Gildar, Jayda Hylton-Pelaia, Jordan Roberts, Jacquelyn Kilbourne and Kaushal Rege, 23 October 2025, Proceedings of the National Academy of Sciences.
DOI: 10.1073/pnas.2415164122
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1 Comment
thanks for this