Identification of genes down-regulated during melanoma progression: a cDNA array study.

In order to identify genes relevant for melanoma development, we carried out cDNA array experiments employing an in vitro model of human melanoma progression, consisting of two cell lines: one, LP, derived from a primary melanoma and the other, LM, from its metastatic supraclavicular lymph node. Basic cDNA array data identified 26 genes as down-regulated in the LM cell line. Northern blot analysis confirmed an effective transcriptional down-regulation for five out of 13 genes analyzed.

The HtrA1 serine protease is down-regulated during human melanoma progression and represses growth of metastatic melanoma cells.

Differential gene expression of cell lines derived from a malignant melanoma or its autologous lymph node metastasis using cDNA arrays indicated down-regulation of PRSS11, a gene encoding the serine protease HtrA1, a homolog of the Escherichia coli protease HtrA, in the metastatic line. Stable PRSS11 overexpression in the metastatic cell line strongly inhibited proliferation, chemoinvasion and Nm23-H1 protein expression in vitro, as well as cell growth in vivo in nu/nu mice. A polyclonal anti-HtrA1 serum demonstrated a significantly higher expression in primary melanomas when compared to unrelated metastatic lesions in a human melanoma tissue array, and down-modulation of HtrA1 expression in autologous lymph node melanoma metastases in seven out of 11 cases examined.