Differential expression of matrix metalloproteinase-2 by fibroblasts in co-cultures with keratinocytes, basal cell carcinoma and melanoma.

To address whether matrix metalloproteinase (MMP)-2 expression by mesenchymal fibroblasts may be differentially modulated by interactions with normal or malignant epidermal cells, we set up a fibroblast co-culture model separately with keratinocytes, basal cell carcinoma cells and melanoma cells. Real-time reverse transcription polymerase chain reaction (RT-PCR) and gelatin zymography were used to detect and quantify the expression of MMP-2 by these different kinds of cells. In independent cultures, MMP-2 was highly expressed by fibroblasts and melanoma cells constitutively, but barely expressed by keratinocytes and basal cell carcinoma (BCC) cells. MMP-2 expression by fibroblasts was downregulated in co-cultures with keratinocytes or BCC cells, but not with melanoma cells. These results indicate that epidermal-mesenchymal interactions are important modulators for MMP-2 expression by cutaneous cells and suggest a host-defense mechanism against the tumor progression of BCC.