RANK Is Expressed in Metastatic Melanoma and Highly Upregulated on Melanoma-Initiating Cells
RANK Is Expressed in Metastatic Melanoma and Highly Upregulated on Melanoma-Initiating Cells
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DOI：
10.1038/jid.2010.377
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发表时间：
2011-04-01
影响因子：
6.5
通讯作者：
Loser, Karin
中科院分区：
文献类型：
--
作者：
Kupas, Verena;Weishaupt, Carsten;Loser, Karin
黑色素瘤占皮肤癌相关死亡的79%，NF-kappa B受体激活因子(RANK)- NF-kappa B配体受体激活因子（RANKL）通路已被证明参与上皮肿瘤细胞的迁移和转移。在这项研究中，我们证明，与来自I期黑色素瘤患者的肿瘤细胞相比，来自IV期黑色素瘤患者的外周血循环黑色素瘤细胞、原发性黑色素瘤和转移瘤中的RANK显著升高。然而，与未发生骨转移的IV期黑色素瘤患者相比，伴有骨转移的IV期黑色素瘤患者未发现RANK表达上调，这可能解释了临床观察到黑色素瘤细胞不优先转移到骨组织。引人注目的是，来自外周血、原发性肿瘤或IV期患者转移的表达rank的黑色素瘤细胞共表达atp结合盒（ABC） B5和CD133，这两种标记物都是黑色素瘤起始细胞的特征，表明肿瘤干细胞样表型。为了支持这一假设，与来自同一患者的RANK（-）黑色素瘤细胞相比，表达RANK的黑色素瘤细胞显示出降低的Ki67增殖指数，并且能够诱导免疫缺陷小鼠的肿瘤生长。总之，我们的数据表明，RANK在转移性黑色素瘤中表达增加，在黑色素瘤起始细胞中表达高度上调，这表明RANK可能参与黑色素瘤起始细胞的发育和维持，并可能参与转移性扩散。Journal of Investigative Dermatology (2011) 131, 944-955；doi: 10.1038 / jid.2010.377;2011年1月27日在线发布
Melanoma accounts for similar to 79% of skin cancer-related deaths, and the receptor activator of NF-kappa B (RANK)-receptor activator of NF-kappa B ligand (RANKL) pathway has been shown to be involved in the migration and metastasis of epithelial tumor cells. In this study, we demonstrate that RANK was significantly increased in peripheral circulating melanoma cells, primary melanomas, and metastases from stage IV melanoma patients compared with tumor cells from stage I melanoma patients. However, upregulated RANK expression was not found in stage IV melanoma patients with bone metastases compared with stage IV melanoma patients without bone metastases, providing a possible explanation for the clinical observation that melanoma cells do not preferentially metastasize to bone tissue. Strikingly, RANK-expressing melanoma cells from peripheral blood, primary tumors, or metastases of stage IV patients coexpressed ATP-binding cassette (ABC) B5 and CD133, both markers characteristic of melanoma-initiating cells, suggesting a tumor stem cell-like phenotype. In support of this hypothesis, RANK-expressing melanoma cells showed a reduced Ki67 proliferation index compared with RANK(-) melanoma cells from the same patient and are able to induce tumor growth in immunodeficient mice. Together, our data demonstrate that RANK expression is increased in metastatic melanoma and highly upregulated on melanoma-initiating cells, suggesting that RANK might be involved in the development and maintenance of melanoma-initiating cells and possibly in metastatic spreading. Journal of Investigative Dermatology (2011) 131, 944-955; doi:10.1038/jid.2010.377; published online 27 January 2011