The fate of human malignant melanoma cells transplanted into zebrafish embryos: Assessment of migration and cell division in the absence of tumor formation
The fate of human malignant melanoma cells transplanted into zebrafish embryos: Assessment of migration and cell division in the absence of tumor formation
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DOI：
10.1002/dvdy.20471
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发表时间：
2005-08-01
影响因子：
2.5
通讯作者：
Hendrix, MJC
中科院分区：
文献类型：
--
作者：
Lee, LMJ;Seftor, EA;Hendrix, MJC
某些侵袭性黑色素瘤细胞系表现出去分化表型，表达各种细胞类型（包括内皮细胞、神经细胞和干细胞）的特征性基因。此外，我们已经表明，侵袭性黑色素瘤细胞可以参与体内新血管形成和体外血管生成拟态，表明这些细胞对微环境的线索和表现发育可塑性。为了进一步探索这种可塑性，我们将人类转移性黑色素瘤细胞移植到斑马鱼囊胚期胚胎中，并监测它们移植后的行为。数据显示，放置在斑马鱼胚胎中的人转移性黑色素瘤细胞存活，表现出运动性和分裂。黑色素瘤细胞不会形成肿瘤，也不会整合到宿主器官中，而是分散在整个胚胎的间隙中，反映了癌细胞的去分化状态。与黑色素瘤细胞的命运相反，移植到斑马鱼胚胎中的人类黑色素细胞最常分布到其正常的皮肤微环境中，这表明斑马鱼胚胎含有可以被正常人类细胞解释的可能的归巢线索。最后，我们表明，在斑马鱼胚胎，转移性黑色素瘤细胞保留其去分化表型。这些结果证明了斑马鱼胚胎模型用于研究肿瘤细胞可塑性的实用性，并表明该实验范例可以是研究肿瘤微环境的有力范例（c）2005 Wiley-Liss，Inc.
Certain aggressive melanoma cell lines exhibit a dedifferentiated phenotype, expressing genes that are characteristic of various cell types including endothelial, neural, and stem cells. Moreover, we have shown that aggressive melanoma cells can participate in neovascularization in vivo and vasculogenic mimicry in vitro, demonstrating that these cells respond to microenvironmental cues and manifest developmental plasticity. To explore this plasticity further, we transplanted human metastatic melanoma cells into zebrafish blastula-stage embryos and monitored their behavior post-transplantation. The data show that human metastatic melanoma cells placed in the zebrafish embryo survive, exhibit motility, and divide. The melanoma cells do not form tumors nor integrate into host organs, but instead become scattered throughout the embryo in interstitial spaces, reflecting the dedifferentiated state of the cancer cells. In contrast to the fate of melanoma cells, human melanocytes transplanted into zebrafish embryos most frequently become distributed to their normal microenvironment of the skin, revealing that the zebrafish embryo contains possible homing cues that can be interpreted by normal human cells. Finally, we show that within the zebrafish embryo, metastatic melanoma cells retain their dedifferentiated phenotype. These results demonstrate the utility of the zebrafish embryonic model for the study of tumor cell plasticity and suggest that this experimental paradigm can be a powerful one in which to investigate tumor-microenvironment (c) 2005 Wiley-Liss, Inc.