Expression of urokinase-type plasminogen activator and its receptor in keloids.
BACKGROUND
The urokinase-mediated plasminogen activation (uPA) system plays a central role in a number of cellular processes including tissue remodeling, cell migration, and angiogenesis. Elevated uPA activity has also been seen with tumor invasion and metastasis in a variety of malignancies. Keloids represent an aberrant form of wound healing characterized by uncontrolled growth with invasion beyond the margins of the original wound. The regulation of this cellular process remains poorly understood. We hypothesize that keloids will have increased staining percentage for uPA and its receptor (uPAR) compared with normal scars. To our knowledge, no previous studies have examined the relationship of uPAR in keloid formation.


METHODS
Analysis of uPAR expression by immunohistochemistry in paraffin sections from 20 keloids and 18 normal scars. Expression was graded by a dermatopathologist according to percentage of cells staining for uPAR.


METHODS
University Medical Center (Division of Otolaryngology-Head and Neck Surgery) and the Department of Dermatology at the University of Rochester Medical and Dental School, Rochester, NY.


RESULTS
Of the 20 keloids, 8 (40%) strongly expressed uPAR (>50% of cells), while only 4 (22%) of 18 normal scars had similar staining. More than half of the normal scars stained minimally for uPAR (<5% staining). There was a strong expression of uPAR in the extracellular matrix in 14 (70%) of the 20 keloids, while no scar showed uPAR in the extracellular matrix.


CONCLUSIONS
Our observation suggests that the uPA system is involved in the expansion of keloids beyond the wound margins in part through the degradation of the extracellular matrix, a finding that is supported by the strong expression of uPAR in the extracellular matrix and collagenous cords in most keloids studied.
Leake
Deirdre
D
Division of Otolaryngology-Head and Neck Surgery, University of Rochester School of Medicine and Dentistry, 601 Elmwood Drive, Rochester, NY 14642, USA. deirdreleake@hotmail.com
Doerr
Timothy D
TD
Scott
Glynis
G
D002465:Cell Movement; D002921:Cicatrix / Q000201:enzymology / Q000473:pathology*; D015986:Confounding Factors, Epidemiologic; D005109:Extracellular Matrix / Q000737:chemistry; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007627:Keloid / Q000201:enzymology / Q000473:pathology*; D018919:Neovascularization, Physiologic; D011956:Receptors, Cell Surface / Q000032:analysis* / Q000037:antagonists & inhibitors / Q000502:physiology*; D055293:Receptors, Urokinase Plasminogen Activator; D012189:Retrospective Studies; D016037:Single-Blind Method; D013997:Time Factors; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis* / Q000037:antagonists & inhibitors / Q000502:physiology*; D014945:Wound Healing
C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator