Ahmed N U, Ueda M, Ito A, Ohashi A, Funasaka Y, Ichihashi M
Department of Dermatology, Kobe University School of Medicine, Japan.
Melanoma Res. 1997 Aug;7(4):299-305. doi: 10.1097/00008390-199708000-00004.
In a previous study, we showed by immunohistochemical analysis that basic fibroblast growth factor (bFGF) is expressed strongly and homogeneously in naevus-cell naevus (NCN), while that in malignant melanoma (MM) is heterogeneous and sometimes non-existent. In order to elucidate the role of bFGF in these pigmented tumours, the expression of its receptors must be determined. In this study, we performed an immunohistochemical analysis of FGF receptors 1, 2 and 3 (FGFR-1, FGFR-2 and FGFR-3, respectively) in NCN and MM and compared their expression and localization with those of bFGF. The expression of bFGF and its three receptors was also examined in melanoma cell lines. None of the 10 NCN that showed strong, homogeneous staining for bFGF expressed FGFR-1 or FGFR-3 proteins; six weakly expressed FGFR-2 protein. Ten primary and 10 metastatic MM showed heterogeneous expression for the three receptors, with larger populations of FGFR-3-negative cells in the primary than in the metastatic tumours. Western blot analysis showed homogeneous expression of bFGF protein in all four melanoma cell lines tested, while FGFR proteins had a heterogeneous distribution in the different cell lines. Cultured NCN and normal melanocytes showed no immunoreactive band for FGFR-1 protein, the only protein tested. Our results suggested that tumour-derived bFGF is involved in melanoma formation through an autocrine mechanism, but is involved mostly through a paracrine or other mechanisms in NCN.
在之前的一项研究中，我们通过免疫组织化学分析表明，碱性成纤维细胞生长因子（bFGF）在痣细胞痣（NCN）中强烈且均匀地表达，而在恶性黑色素瘤（MM）中则是异质性的，有时甚至不存在。为了阐明bFGF在这些色素性肿瘤中的作用，必须确定其受体的表达情况。在本研究中，我们对NCN和MM中的成纤维细胞生长因子受体1、2和3（分别为FGFR-1、FGFR-2和FGFR-3）进行了免疫组织化学分析，并将它们的表达和定位与bFGF的表达和定位进行了比较。我们还检测了黑色素瘤细胞系中bFGF及其三种受体的表达情况。10例对bFGF呈强而均匀染色的NCN均未表达FGFR-1或FGFR-3蛋白；6例弱表达FGFR-2蛋白。10例原发性和10例转移性MM对这三种受体呈异质性表达，原发性肿瘤中FGFR-3阴性细胞的比例高于转移性肿瘤。蛋白质印迹分析表明，在所有检测的四种黑色素瘤细胞系中bFGF蛋白表达均匀，而FGFR蛋白在不同细胞系中的分布是异质性的。培养的NCN和正常黑素细胞对所检测的唯一蛋白FGFR-1蛋白未显示免疫反应条带。我们的结果表明，肿瘤来源的bFGF通过自分泌机制参与黑色素瘤的形成，但在NCN中主要通过旁分泌或其他机制发挥作用。
