Ganglioside Profiles of Merkel Cell Carcinoma
Merkel cells are located mainly in the epidermis and considered to have a regulatory role in the growth and differentiation of keratinocytes. On account of their biological behavior, Merkel cells are thought to belong to “paraneurons”(Fujita 1989). Althou
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Summary Merkel cells are located mainly in the epidermis and considered to have a regulatory role in the growth and differentiation of keratinocytes. On account of their biological behavior, Merkel cells are thought to belong to "paraneurons"(Fujita 1989). Although many kinds of functions of these cells have been clarified, their origin is still unknown. Therefore, we analyzed the ganglioside compositions of Merkel cell carcinomas in order to discuss their origin and metastatic potency.
Introduction Gangliosides (sialylated glycosphingolipids) are components of mammalian plasma membranes and show quantitative and qualitative differences in their expression in different tissues. Many biological functions of gangliosides are known, such as growth regulation, cell differentiation, cell-substrate interaction, etc. Previously, we reported that GD3, a disialoganglioside, might play a role in the proliferation and metastasis ofhuman malignant melanoma (Nakano 1996). For a long time, Merkel cells have only been considered to be mechanoreceptors in the skin. However, many studies have revealed that they play a regulatory function in the development of epidermis and appendages during the fetal period (Narisawa 1993; Kim 1995). These behaviors resemble those of neuroendocrine cells. On the other hand, electron microscope studies suggest that Merkel cells might be derived from the epidermis (Munger 1965). Merkel cell carcinoma is an uncommon malignant tumor which often occurs on the head and neck. This tumor sometimes metastases to lymph nodes or distant organs, but is considered to show better prognosis compared to malignant melanoma.
K. I. Baumann et al. (eds.), The Merkel Cell © Springer-Verlag Berlin Heidelberg 2003
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Nagai et aL
Patients and Control Materials Two Japanese patients with Merkel cell carcinoma underwent excisional treatment in the Dermatology Clinic, Yamaguchi University Hospital. One was an 82year-old female who had a dark red nodule on her right cheek. Another patient was a 58-year-old male who had a nodule on his chest. In both cases, the diagnosis was performed by routine pathological and immunohistochemical techniques. The specimens of Merkel cell carcinoma were stored at -80 oc until ganglioside analyses were performed. As controls, specimens obtained from nevus cell nevus, malignant melanoma, neurofibroma and dermatofibroma protuberans were also examined.
Isolation and Analysis of Gangliosides Resected tumors were mashed and extracted with chloroform-methanol(2:1, 1:1, 1:2, vol/vol, sequentially). Then the glycolipid fraction was isolated by Florisil chromatography of acetylated derivatives. Neutral glycolipids were separated from gangliosides by DEAE-Sephadex A-50 ion exchange chromatography (Pharmacia ILKB, Piscataway, NJ). The ganglioside fraction was isolated by chromatography on a Sep-Pak C18 (Waters-Millipore, Milford, MA). Ganglioside composition was analyzed by thin-layer chromatography (TLC). TLC was performed in chloroform-methanol-0.2% CaCl (55:45:10) on high performance TLC plates
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