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. These results suggest that down-regulation of PRSS11 and HtrA1 expression may represent an indicator of melanoma progression.
Baldi
Alfonso
A
Laboratory 'C', CRS, Regina Elena Cancer Institute, Rome, Italy.
De Luca
Antonio
A
Morini
Monica
M
Battista
Tullio
T
Felsani
Armando
A
Baldi
Feliciano
F
Catricalà
Caterina
C
Amantea
Ada
A
Noonan
Douglas M
DM
Albini
Adriana
A
Natali
Pier Giorgio
PG
Lombardi
Daniela
D
Paggi
Marco G
MG
D000818:Animals; D002874:Chromosome Mapping; D015536:Down-Regulation; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007150:Immunohistochemistry; D008545:Melanoma / Q000201:enzymology* / Q000473:pathology / Q000556:secondary; D011817:Rabbits; D012697:Serine Endopeptidases / Q000032:analysis / Q000235:genetics*
D012697:Serine Endopeptidases