Van Belle P, Rodeck U, Nuamah I, Halpern A C, Elder D E
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia 19104, USA.
Am J Pathol. 1996 Jun;148(6):1887-94.
Melanocytic neoplasia is characterized by the aberrant overproduction of multiple cytokines in vitro. However, it is largely unknown how cytokine expression relates to melanoma progression in vivo. Transforming growth factor beta (TGF-beta) is a multifunctional cytokine commonly produced by cultured melanoma cells. The in situ expression of all three TGF-beta isoforms (TGF-beta1, -2, and -3) was determined immunohistochemically in melanocytes and in 51 melanocytic lesions using isoform-specific antibodies. Significant linear trends of expression were observed from melanocytes through nevi and primary and metastatic melanomas for all three isoforms. TGF-beta1 was expressed by some melanocytes and almost uniformly by nevi and melanomas. TGF-beta2 and -3 were not expressed in normal melanocytes but were expressed in nevi and early and advanced primary (radial and vertical growth phase) and metastatic melanomas in a tumor-progression-related manner. TGF-beta2 was heterogeneously expressed in advanced primary and metastatic melanomas, whereas TGF-beta3 was uniformly and highly expressed in these lesions. Thus, expression of TGF-beta isoforms in melanocytes and melanocytic lesions is heterogeneous and related to tumor progression, and expression of TGF-beta2 and TGF-beta3 commences at critical junctures during progression of nevi to primary melanomas.
黑素细胞肿瘤形成的特征是在体外多种细胞因子异常过量产生。然而，细胞因子表达与体内黑色素瘤进展之间的关系在很大程度上尚不清楚。转化生长因子β（TGF-β）是培养的黑色素瘤细胞通常产生的一种多功能细胞因子。使用同工型特异性抗体，通过免疫组织化学方法测定了黑素细胞和51个黑素细胞性病变中所有三种TGF-β同工型（TGF-β1、-2和-3）的原位表达。对于所有三种同工型，从黑素细胞到痣、原发性和转移性黑色素瘤均观察到显著的线性表达趋势。TGF-β1由一些黑素细胞表达，痣和黑色素瘤几乎均一表达。TGF-β2和-3在正常黑素细胞中不表达，但在痣以及早期和晚期原发性（放射状和垂直生长期）和转移性黑色素瘤中以与肿瘤进展相关的方式表达。TGF-β2在晚期原发性和转移性黑色素瘤中呈异质性表达，而TGF-β3在这些病变中呈均一性高表达。因此，TGF-β同工型在黑素细胞和黑素细胞性病变中的表达是异质性的，且与肿瘤进展相关，TGF-β2和TGF-β3的表达在痣向原发性黑色素瘤进展的关键节点开始。
