Induction of Hsp90 protein expression in malignant melanomas and melanoma metastases.
The heat-shock protein Hsp90 has been shown to be essential for the functional integrity of the telomerase complex. The telomerase activity is enhanced in melanoma and stabilizes the chromosomal integrity in proliferating cells. Furthermore, overexpression of Hsp90 induces silencing of point mutations in transcription factors which, otherwise, would result in a loss-of-function phenotype. In melanocytic lesions there is a higher risk of mutations caused by the enhanced proliferation in melanocytic cells. By analyzing microdissected melanocytic tumors by semiquantitative PCR, we demonstrate an overexpression of Hsp90 mRNA in malignant melanomas (10/14) and in melanoma metastases (6/6) as well as in melanoma cell lines (9/9) when compared with melanocytic nevi (2/9). These results could be confirmed on protein level by immunohistochemistry. While melanocytic nevi show discrete Hsp90 expression only in a minor fraction (2/9), malignant melanomas and metastases show a positive Hsp90 immunohistochemistry in the majority of cases; (7/9) and (13/14), respectively. In addition, by analyzing melanoma metastases by flow cytometry we show that Hsp90 is expressed on the surface of tumor cells (7/8). From these data we conclude that Hsp90 is present in advanced malignant melanomas and may have a stabilizing effect on the cellular functions in proliferating cells of melanocytic lesions and could thereby be a prerequisite for the tumor progression. As Hsp90 is expressed on the cell surface, it might also be a potential immunorelevant target structure for immunotherapy of melanoma.
Department of Dermatology, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany. bernd.becker@klinik.uni-regensburg.de
B
B
Becker
G
G
Multhoff
B
B
Farkas
P-J
PJ
Wild
M
M
Landthaler
W
W
Stolz
T
T
Vogt
D001706:Biopsy; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008545:Melanoma / Q000235:genetics* / Q000473:pathology*; D009362:Neoplasm Metastasis / Q000235:genetics; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018841:HSP90 Heat-Shock Proteins; D012333:RNA, Messenger