Keloids and hypertrophic scars are sequelae of abnormal healing after orofacial injury. These conditions represent debilitating derangements in remodeling and are associated with impaired function and significant dysmorphea. They are defined largely by an abnormal accumulation of extracellular matrix. Recently, remarkable similarities have been found between the generation of tumor stroma and the healing of wounds.
The aim of this pilot study is to investigate whether keloids are the result of a trauma-induced neoplastic process or simply an inflammatory response to injury; this will be accomplished by studying expression by abnormal scar tissues of CD44 variant isoforms, known markers for neoplastic tissue.
The specific aims are: 1. To survey tissues derived from normal skin (NSk), normal scar (NSc), hypertrophic scar (HSc) and keloid for variant CD44 isoforms known to be markers for neoplastic lesions. 2. To synthesize cDNA probes for the different CD44 variant isoforms found in neoplastic lesions and to use them to assess variant isoform gene expression. Briefly tissues obtained from human NSk, NSc, HSc and keloids will be screened by immunohistochemistry techniques for CD44 variant isoforms using specific antibodies against these molecules. Also, cDNA probes for the various CD44 isoforms will be synthesized, in order to study their gene expression by these tissues using Northern blot analysis and in situ hybridization. These findings will aid in understanding the pathogenesis of keloid formation and whether it is a trauma-induced neoplastic process or a reactive response to injury. In either case, if CD44 variant isoforms are present and expressed differentially in cases of normal versus abnormal scar tissues, these results are expected to lead to additional studies using variant-specific CD44 monoclonal antibodies as tools in developing new strategies for diagnosis and, perhaps, treatment of hypertrophic scars and keloids. Most importantly, this work as potential for offering new insight into the basic biology of abnormal scar formation in minorities.
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