de Waard Nadine E, Kolovou Paraskevi E, McGuire Sean P, Cao Jinfeng, Frank Natasha Y, Frank Markus H, Jager Martine J, Ksander Bruce R
Department of Ophthalmology, Schepens Eye Research Institute and Massachusetts Eye and Ear Infirmary, Boston, Mass., USA ; Department of Ophthalmology, LUMC, Leiden, The Netherlands.
Department of Ophthalmology, Schepens Eye Research Institute and Massachusetts Eye and Ear Infirmary, Boston, Mass., USA.
Ocul Oncol Pathol. 2015 Apr;1(3):182-189. doi: 10.1159/000371555.
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- /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.
结膜黑色素瘤（CM）是一种罕见的眼部恶性肿瘤，具有较高的局部复发倾向和发生转移性疾病的高风险。转移灶通常对传统治疗无反应。最近，利用人CM细胞建立了一种动物模型。通过将三种不同的CM细胞系结膜下注射到NOD.Cg- /SzJ（NSG）小鼠体内，创建了人CM的原位异种移植模型。结膜下注射培养的CM细胞导致结膜下生长良好，但未发现转移。当从结膜下异种移植中获得单细胞悬液并在体内传代时，所有小鼠都发生了转移。由于最近的研究结果表明癌症干细胞与肿瘤复发有关，我们利用这个新的小鼠模型来确定干细胞标志物ABCB5在肿瘤进展过程中的表达。在我们的模型中，在三种细胞系以及肿瘤发展的不同阶段测定了ABCB5蛋白的表达。所有三种细胞系都含有ABCB5阳性的细胞亚群。在肿瘤发展过程中，ABCB5的表达在肿瘤扩张阶段增加。此外，转移灶中ABCB5的表达也增加。利用这个CM模型，我们能够启动转移扩散，并确定干细胞标志物ABCB5在肿瘤发展不同阶段的表达，将ABCB5确定为一个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。
