Journal
CANCER RESEARCH
Volume 69, Issue 22, Pages 8662-8669Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-09-1099
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Funding
- Dermatology Foundation
- Astellas Pharma U.S. Research Endowment
- Kingsley pharmaceutical Incorporations Research Educational Endowment
- National Natural Science Foundation of China [30672753]
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We have recently discovered that de-N-acetyl GM3 [NeuNH(2)-LacCer, d-GM3], a derivative of ganglioside GM3, is specifically expressed in metastatic tumor cells and that its expression correlates with an enhanced metastatic phenotype. Although the classic N-acetylated form of GM3 (NeuAcLacCer, c-GM3) is found in both normal and tumor cells, metastatic tumor cells of (but not other cells) predominantly express d-GM3 (82-95% of total GM3). d-GM3 expression is mainly found in metastatic melanomas, but not in benign nevi or the majority of primary melanomas. Using metastatic (d-GM3-positive) and poorly invasive (d-GM3-negative) human melanoma cell lines, we found that d-GM3 stimulates cell migration and invasion by increasing the expression and activation of urokinase-like plasminogen activator (uPA). Further studies showed that d-GM3 activates matrix metalloproteinase-2 (MMP-2), but not MMP-9, when uPA receptor signaling is activated. These results implicate d-GM3 as a specific marker for metastatic melanoma and a novel therapeutic target for neoplastic diseases. [Cancer Res 2009;69(22):8662-9]
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