Growth and
metastasis of solid
neoplasms require the recruitment of a supporting
tumor stroma. A highly consistent trait of
tumor stromal fibroblasts in most epithelial
cancers is the induction of fibroblast activation
protein (FAP), a member of the
serine protease family. Recently it was demonstrated that FAP has both
dipeptidyl peptidase and collagenolytic activity capable of degrading
gelatin and
type I collagen. In this study, we describe the expression and
enzyme activity of FAP in benign and malignant melanocytic skin
tumors. FAP-positive fibroblasts were detected immunohistochemically in the reactive stroma of all
melanocytic nevi tested. In primary and metastatic
melanomas an upregulation of FAP expression in the reactive mesenchyme could be observed. Whereas 30% of the
nevi revealed additional FAP expression on subsets of melanocytic cells,
melanoma cells from primary and metastatic
melanomas were FAP negative. This may indicate a possible role for FAP in the control of
tumor cell growth and proliferation during
melanoma carcinogenesis. Consistent with this in vivo expression pattern FAP
enzyme activity could be detected by a specific immunocapture assay in extracts of
melanocytic nevi and
melanoma metastases, whereas no significant activity was detectable in normal adult skin. Strong
protein expression of FAP was observed in patterned structures restricted to a subset of the
melanoma metastases. Our findings that these FAP-positive structures showed no overlap with endothelial cell surface markers, nor with various
melanoma antigens, suggest that FAP is a marker for specific stromal-cell-derived patterns in cutaneous
melanoma metastases.