Expression of microtubule-associated protein 2 in benign and malignant melanocytes -: Implications for differentiation and progression of cutaneous melanoma
Expression of microtubule-associated protein 2 in benign and malignant melanocytes -: Implications for differentiation and progression of cutaneous melanoma
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DOI：
10.1016/s0002-9440(10)64682-2
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发表时间：
2001-06-01
影响因子：
6
通讯作者：
Setaluri, V
中科院分区：
文献类型：
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作者：
Fang, D;Hallman, J;Setaluri, V
皮肤黑素细胞肿瘤已知获得神经嵴分化的可变特征。真皮中的黑素细胞痣细胞和促纤维增生性黑色素瘤常表现出神经鞘分化的特征。原发性和转移性黑色素瘤细胞所显示的神经元分化特征的程度和性质尚不清楚。在此，我们描述了通过分化诱导剂β-二乙酰胺在培养的转移性黑色素瘤细胞中诱导微管相关蛋白2（MAP-2c）的幼年同种型，该MAP-2同种型的上调，该MAP-2同种型是未成熟神经元的标志物，伴随着延长的树突状形态和酪氨酸酶相关蛋白1（TYRP 1/gp 75）（黑素细胞分化标志物）的下调。在一组代表黑色素瘤肿瘤进展的细胞系中，MAP-2c mRNA和相应的类似于70-kd的蛋白质主要在原发性黑色素瘤中检测到。61例良恶性黑素细胞病变的免疫组化分析显示，MAP-2蛋白在黑素细胞痣和原发性黑色素瘤的原位和侵袭性成分中表达丰富，但在少数转移性黑色素瘤中仅灶性异质表达。相反，MAP-2阳性的真皮痣细胞和原发性黑素瘤的侵袭性细胞是TYRP 1阴性的。这种体内相互染色模式与体外观察相似，即在转移性黑素瘤细胞中诱导神经元标记物MAP-2伴随着黑素细胞标记物TYRP 1的选择性消失。我们的数据表明，肿瘤性黑素细胞，特别是在早期阶段，保持表达神经元特异性标记物MAP-2的可塑性。这些观察结果与真皮中的良性和恶性黑素细胞都可以表达神经元分化的标记物的前提一致。
Cutaneous melanocytic neoplasms are known to acquire variable characteristics of neural crest differentiation. Melanocytic nevus cells in the dermis and desmoplastic melanomas often display characteristics of nerve sheath differentiation. The extent and nature of neuronal differentiation characteristics displayed by primary and metastatic melanoma cells are not well understood, Here, we describe induction of a juvenile isoform of microtubule-associated protein 2 (MAP-2c) in cultured metastatic melanoma cells by the differentiation inducer hexamethylene bisacetamide, Up-regulation of this MAP-2 isoform, a marker for immature neurons, is accompanied by extended dendritic morphology and down-regulation of tyrosinase-related protein 1 (TYRP1/gp75), a melanocyte differentiation marker. In a panel of cell lines that represent melanoma tumor progression, MAP-2c mRNA and the corresponding similar to 70-kd protein could be detected predominantly in primary melanomas. Immunohistochemical analysis of 61 benign and malignant melanocytit lesions showed abundant expression of MAP-2 protein in melanocytic nevi and in the in situ and invasive components of primary melanoma, but only focal heterogeneous expression in a few metastatic melanomas. In contrast, MAP-2-positive dermal nevus cells and the invasive cells of primary melanomas were TYRP1-negative, This reciprocal staining pattern in vivo is similar to the in vitro observation that induction of the neuronal marker MAP-2 in metastatic melanoma cells is accompanied by selective extinction of the melanocytic marker TYRP1, Our data show that neoplastic melanocytes, particularly at early stages, retain the plasticity to express the neuron-specific marker MAP-2. These observations are consistent with the premise that both benign and malignant melanocytes in the dermis can express markers of neuronal differentiation.