Cisplatin Induces the Giant Cells Formation in Melanoma Cells in vitro and in vivo

• Main Authors: Chien-hui Weng, 翁千惠
• Other Authors: Chen-Fu Shaw
• Format: Others
• Language: en_US
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/97887189626855894272

博士 === 國立中山大學 === 生物科學系研究所 === 101 === Melanoma, which is the most aggressive form of skin cancer, is notoriously resistant to current cancer therapies. Cisplatin is a first-line chemotherapy drug for melanoma. However, the chemoresistance mechanism of melanoma cells to cisplatin therapy remains unclear. In this study, we investigated the morphological changes that are mediated by cisplatin in B16-F10 melanoma cells and the relationship between these changes and chemoresistances/cancer stemness. We observed that cisplatin enhanced the formation of giant cells, which exhibit increased cell surface and nuclear areas. Through confocal laser-scanning microscopy, we found that the giant cells exhibited reduced cell thickness and motilities. More importantly, the formation of melanocytic malignancy maker S100-positive giant cells was also found in cisplatin-treated melanoma in vivo. Expression analyses revealed that the giant cells were positive for the proliferation marker Ki-67 and expressed the melanoma stem cell markers ABCB5 and CD133 in vitro and in vivo. Through mitochondria tracking and JC-1 staining, we showed that the cisplatin-induced giant cells exhibit elevated mitochondria genesis and activities and increased levels of ATP synthesis. These results indicate the high energy demand of these giant cells. In summary, this study presents a novel cellular event that melanoma cells enlarge their cell size in response to cisplatin. Furthermore, these giant cells exhibit molecular markers and functions of cancer stem cells, which may be useful for the histopathologic examination of cancer stem cells. Finally, the targeting at the metabolic demand of giant cells may facilitate a novel anti-neoplastic strategy against melanoma.