Tumour endothelial marker-8 in wound healing and its impact on the proliferation and migration of keratinocytes

Chronic wound management represents a significant burden on healthcare systems and negatively impacts on the quality of patient life. New strategies to understand and identify wounds that will not heal in a normal manner are required. Tumour endothelial marker-8 (TEM-8) has been implicated in the wound healing and angiogenesis processes. TEM-8 expression was examined at the transcript level in a cohort of acute (n=10) and chronic (n=14) wounds and in normal skin (n=10). Protein analysis of TEM-8 was also undertaken for this cohort using immunohistochemistry (IHC). TEM-8 impact on keratinocyte cell growth and migration was assessed following TEM-8 ribozyme transgene transfection of human HaCaT keratinocytes using cell growth and electric cell-substrate impedance sensing (ECIS)-based assays. Expression of TEM-8 was observed to be increased in acute wounds compared to chronic wounds and normal skin using quantitative polymerase chain reaction transcript analysis and IHC staining of wound tissues. Knockdown of TEM-8 in HaCaT cells, using two independent ribozyme transgenes, resulted in significant decreases in cell growth as well as reductions in the rate of migration assessed using an ECIS-based system. TEM-8 may be differentially expressed between wound types and loss of this molecule impacts HaCaT growth and migration, potentially implicating this molecule as a factor involved in successful progression of wound healing.