Identification of glypican-3 as a novel tumor marker for melanoma.

Abstract

PURPOSE:

We reported recently the novel tumor marker glypican-3 (GPC3) for hepatocellular carcinoma. In the present study, we investigated the expression of GPC3 in human melanoma cell lines and tissues and asked whether GPC3 could be a novel tumor marker for melanoma.

EXPERIMENTAL DESIGN:

Expression of GPC3 mRNA and protein was investigated in human melanoma cell lines and tissues using reverse transcription-PCR and immunohistochemical analysis. Secreted GPC3 protein was quantified using ELISA in culture supernatants of melanoma cell lines and in sera from 91 patients with melanoma and 28 disease-free patients after surgical removal of primary melanoma. All of the subjects were Japanese nationals.

RESULTS:

In >80% of melanoma and melanocytic nevus, there was evident expression of GPC3 mRNA and protein. Furthermore, GPC3 protein was evidenced in sera of 39.6% (36 of 91) of melanoma patients but not in sera from subjects with large congenital melanocytic nevus (0 of 5) and from healthy donors (0 of 60). Twenty-seven of 36 serum GPC3-positive patients were negative for both serum 5-S-cysteinyldopa and melanoma-inhibitory activity, well-known tumor markers for melanoma. The positive rate of serum GPC3 (39.6%) was significantly higher than that of 5-S-cysteinyldopa (26.7%) and of melanoma-inhibitory activity (20.9%). Surprisingly, we detected serum GPC3 even in patients with stage 0 in situ melanoma. The positive rate of serum GPC3 at stage 0, I, and II (44.4%, 40.0%, and 47.6%) was significantly higher than that of 5-S-cysteinyldopa (0.0%, 8.0%, and 10.0%). Also observed was the disappearance of GPC3 protein in sera from 11 patients after surgical removal of the melanoma.

CONCLUSIONS:

GPC3 is apparently a novel tumor marker useful for the diagnosis of melanoma, especially in early stages of the disorder.

• Authors: Tetsuya Nakatsura, Toshiro Kageshita, Shosuke Ito, Kazumasa Wakamatsu, Mikio Monji, Yoshiaki Ikuta, Satoru Senju, Tomomichi Ono, Yasuharu Nishimura
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 10 Issue 19 Pg. 6612-21 (Oct 01 2004) ISSN: 1078-0432 [Print] United States
• PMID: 15475451 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• Glypicans
• Heparan Sulfate Proteoglycans
• RNA, Messenger

Topics

• Adult
• Aged
• Aged, 80 and over
• Animals
• Biomarkers, Tumor (analysis, genetics)
• Cell Line, Tumor
• Female
• Gene Expression Regulation, Neoplastic
• Glypicans
• Heparan Sulfate Proteoglycans (analysis, blood, genetics)
• Humans
• Immunohistochemistry
• Male
• Melanoma (genetics, metabolism, pathology)
• Mice
• Middle Aged
• NIH 3T3 Cells
• Neoplasm Staging
• RNA, Messenger (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction