Abstract
Syndecan-2, a transmembrane heparan sulfate proteoglycan, is a critical mediator in the tumorigenesis of colon carcinoma cells. We explored the function of syndecan-2 in melanoma, one of the most invasive types of cancers, and found that the expression of this protein was elevated in tissue samples from both nevus and malignant human melanomas but not in melanocytes of the normal human skin tissues. Similarly, elevated syndecan-2 expression was observed in various melanoma cell lines. Overexpression of syndecan-2 enhanced migration and invasion of melanoma cells, whereas the opposite was observed when syndecan-2 levels were knocked down using small inhibitory RNAs. Syndecan-2 expression was enhanced by fibroblast growth factor-2, which is known to stimulate melanoma cell migration; however, alpha-melanocyte-stimulating hormone decreased syndecan-2 expression and melanoma cell migration and invasion in a melanin synthesis-independent manner. Furthermore, syndecan-2 overexpression rescued the migration defects induced by alpha-melanocyte-stimulating hormone treatment. Together, these data strongly suggest that syndecan-2 plays a crucial role in the migratory potential of melanoma cells.
Highlights
Several reports have linked altered syndecan expression to various elements of cancer cell growth
Syndecan-2 Is Up-regulated in Melanoma Cells—To investigate the role of syndecan-2 in the development of human skin melanoma, the expression of syndecan-2 was compared in tissues obtained from cutaneous malignancies and normal skin
We previously reported that elevated syndecan-2 expression is crucial for tumorigenic activity in colon carcinoma and fibrosarcoma cells [3, 29]
Summary
Several reports have linked altered syndecan expression to various elements of cancer cell growth. Consistent with this observation, elevated cell surface expression of syndecan-2 was observed in human melanoma cell lines (Fig. 2B). Syndecan-2 Regulates Melanoma Cell Migration—Syndecan-2 is known to play a critical role as an adhesion receptor during cell migration. To more directly assess the role of syndecan-2 in the regulation of tumorigenic activity, we examined the effects of syndecan-2 expression on melanoma cell migration.
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