MEL4B3, a novel mRNA is induced in skin tumors and regulated by TGF-beta and pro-inflammatory cytokines

Tumor-stroma interactions play a decisive role in the growth and metastasis of solid tumors, and involve signalling either by soluble mediators or direct cell-cell interaction. Here, we report the isolation and characterisation of a novel cDNA (MEL4B3), which is induced in cultured dermal fibroblasts exposed to supernatants of melanoma cell lines. MEL4B3 shares high homology with two predicted cDNA sequences for which no activity has so far been described. In situ hybridisation revealed the expression of MEL4B3 in malignant melanoma increasing with tumor depth; in basal cell carcinoma and in squamous cell carcinoma. MEL4B3 was barely detectable in normal skin or non-malignant melanocytic naevi. Furthermore, MEL4B3 was expressed at high level in the epidermis of psoriatic skin. In vitro, the expression of MEL4B3 was found to be induced by the exposure of human dermal fibroblasts to melanoma cell culture supernatants or to transforming growth factor-beta, interleukin-1 and tumor necrosis factor-alpha. The expression MEL4B3 therefore reflects closely cell activation occurring during tumor growth, metastasis and inflammation.