Expression of Multidrug Resistance Transporter ABCB5 in a Murine Model of Human Conjunctival Melanoma.
Expression of Multidrug Resistance Transporter ABCB5 in a Murine Model of Human Conjunctival Melanoma.
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DOI：
10.1159/000371555
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发表时间：
2015-04
影响因子：
1
通讯作者：
Ksander BR
中科院分区：
文献类型：
--
作者：
de Waard NE;Kolovou PE;McGuire SP;Cao J;Frank NY;Frank MH;Jager MJ;Ksander BR
结膜黑色素瘤（CM）是一种罕见的眼部恶性肿瘤，具有局部复发的高倾向和转移性疾病的高风险。转移瘤通常对常规治疗无反应。最近，使用人CM细胞建立了动物模型。通过将三种不同的CM细胞系结膜下注射到NOD.Cg-Prkdcscid IL 2 rgtm 1 Wjl/SzJ（NSG）小鼠中来产生来自人CM的原位异种移植物。结膜下注射培养的CM细胞导致结膜下生长良好，但没有发现转移。当从结膜下异种移植物获得单细胞悬液并在体内传代时，所有小鼠均发生转移。由于最近的发现表明癌症干细胞与肿瘤复发有关，我们使用这种新的小鼠模型来确定肿瘤进展过程中干细胞标志物ABCB 5的表达。ABCB 5蛋白的表达在三种细胞系中以及在我们的模型中观察到的肿瘤发展的不同阶段中测定。所有三种细胞系都含有ABCB 5阳性的细胞亚群。在肿瘤发展过程中，ABCB 5的表达在肿瘤扩展阶段增加。此外，ABCB 5的表达增加转移。使用这种CM模型，我们能够启动转移扩散并确定肿瘤发展不同阶段干细胞标志物ABCB 5的表达，将ABCB 5确定为潜在的新型治疗靶点。这项研究说明了我们新建立的小鼠模型的潜力。
Conjunctival melanoma (CM) is a rare ocular malignancy with a high tendency to reoccur locally and with a high risk of metastatic disease. Metastases are often unresponsive to conventional treatment. Recently, an animal model was set up using human CM cells. Orthotopic xenografts from human CM were created by subconjunctival injection of three different CM cell lines into NOD.Cg-Prkdcscid IL2rgtm1Wjl/SzJ (NSG) mice. Subconjunctival injection of cultured CM cells led to excellent subconjunctival growth, but no metastases were found. When single-cell suspensions were obtained from the subconjunctival xenografts and passaged in vivo, all mice developed metastases. As recent findings indicate that cancer stem cells are linked to tumor recurrences, we used this new murine model to determine the expression of the stem cell marker ABCB5 during tumor progression. Expression of the ABCB5 protein was determined in three cell lines and during different stages of tumor development as observed in our model. All three cell lines contained a subpopulation of cells positive for ABCB5. During tumor development, expression of ABCB5 increased during phases of tumor expansion. Furthermore, expression of ABCB5 was increased in metastases. Using this model for CM, we were able to initiate metastatic spread and determine the expression of the stem cell marker ABCB5 during different stages of tumor development, identifying ABCB5 as a potential novel therapeutic target. This study illustrates the potential of our newly established murine model.