New insights in the formation of skin tumors

(07-05-2021) Wounding predisposes tissues to tumor formation. VIB-Ghent University researchers shed new insights in the involvement of cells needed for wound healing, in this process.

VIB researchers under the direction of Prof. Esther Hoste (VIB-UGent) shed new insights in the involvement of specific fibroblasts, cells needed for wound healing, in the fact that wounding predisposes tissues to tumor formation. The scientists show that in tumors that arise at wound sites of the skin fibroblasts with a ‘scarring’ signature are present. One of the top upregulated genes in these cancer-associated fibroblasts is PRSS35, an enzyme known to play a role in scarring. Their research appears today on the cover of the authorative journal EMBO Reports.

Senior author Esther Hoste (VIB-UGent): ‘We now know that enzymes involved in scarring can influence tumor development and should be considered as potential therapeutic targets in cancer treatment.”

Fibroblasts: essential both in wound healing and solid tumors

Chronic wounds and associated inflammation are well-known risk factors for tumor initiation in various tissues. A central role in this phenomenon goes to a specific kind of cells: fibroblasts. On the one hand, fibroblasts are essential for wound healing of the skin by producing collagen. This protein provides strength to the healing tissue, but too much collagen leads to scarring. On the other hand, fibroblasts are an important component of solid tumors.

Esther Hoste says: “We wanted to profile genes that are uniquely expressed in cancer-associated fibroblasts. This would make it possible to identify factors that can tip the balance between normal wound healing, and tumor formation.”

A link between scarring and tumor formation?

For this objective, the researchers made use of a mouse model in which skin wounding results in tumor formation. They profiled the fibroblasts present in the wound-induced tumors and compared them to fibroblasts present in inflamed and normal skin tissues.

“We observed that many proteins that are involved in scarring of the skin, were highly present in the cancer-associated fibroblasts”, says Prof. van Loo. “The enzyme PRSS35, which is known to be important in cleavage of collagen during scar formation, is uniquely expressed in tumor conditions.” Deleting PRSS35 from the skin led to an abnormal collagen composition with thicker collagen fibers in wounds and tumors and surprisingly resulted in the formation of more tumors.
Lisette Van Hove, first author of the study confirms: “Our work demonstrates that enzymes playing a role in scar tissue formation also influence tumor formation.”

PRSS35 as a new biomarker

The research team also investigated the presence of PRSS35 in human skin tumors. They observed that this protein was only present in highly malignant skin tumors.

Prof. Hoste concludes: “We here provide evidence for the use of PRSS35 as a potential biomarker that enables the identification of highly malignant skin tumors. This is important for further clinical care.”

Publication and funding

Fibrotic enzymes modulate wound-induced skin tumorigenesis, Van Hove et al., EMBO Reports
DOI number – 10.15252/embr.202051573

The research was funded bij FWO, CRIG and Stichting tegen Kanker.

Contact

Esther Hoste (VIB-UGent)
Department of Biomedical Molecular Biology
esther.hoste@ugent.be
Mobile: +32 479 50 37 72