Bodey B, Bodey B, Gröger A M, Siegel S E, Kaiser H E
Department of Pathology, School of Medicine, University of Southern California, Los Angeles 91406, USA.
Anticancer Res. 1997 Jan-Feb;17(1A):505-11.
The nm23/NDP kinase gene located on chromosome 17q has been proposed as metastasis suppressor gene in a variety of tumor types. Nm23 was initially isolated from the highly metastatic murine K-1735 melanoma cell line and levels of nm23 have been found to correlate inversely with metastatic potential in some tumors, but not in others. In the present immunocytochemical study, we investigated nm23 protein expression in 30 primary cutaneous malignant melanomas (CMs) and 10 metastases of malignant cutaneous melanomas (MMCMs) which had already metastasized to a distant site. We employed a sensitive, indirect, four to six step alkaline phosphatase conjugated biotin-streptavidin based immunocytochemical technique using the anti-nm23 affinity purified rabbit anti-human polyclonal antibody on formalin fixed paraffin embedded tissue sections of the malignant melanomas. We found nm23 expression in 24 out of 30 CMs with between 10% and 50% of the melanoma cells exhibiting immunoreactivity with the employed antibody. None of the ten MCMMs expressed nm23. As we described in a previous article (48), malignant melanoma is characterized by a high degree of cellular immunophenotype heterogeneity. In further support of this observation, we observed a diverse level of nm23, staining intensity in the cell subpopulations which comprises the tumor microenvironment. Nm23/NDP kinase has a diverse array of biological functions including roles in signal transduction and microtubule assembly. In our opinion, the many roles of nm23/NDP kinase are mainly involved in cell division and this may be the underlying reason that levels of this protein do not truly correlate with metastatic potential. Therefore, nm23 protein levels may correlate well with proliferative rate and degree of tumor specific dedifferentiation which are important parameters to be established in the early diagnosis, monitoring of neoplasma progression and efficacy of employed clinical trials, and the determination of prognosis of every neoplastic disease.
位于17号染色体长臂上的nm23/NDP激酶基因已被认为是多种肿瘤类型中的转移抑制基因。Nm23最初是从具有高转移潜能的小鼠K-1735黑色素瘤细胞系中分离出来的，并且已发现nm23的水平在某些肿瘤中与转移潜能呈负相关，但在其他肿瘤中并非如此。在本免疫细胞化学研究中，我们调查了30例原发性皮肤恶性黑色素瘤（CMs）和10例已发生远处转移的恶性皮肤黑色素瘤转移灶（MMCMs）中nm23蛋白的表达情况。我们采用了一种灵敏的、间接的、基于碱性磷酸酶偶联生物素-链霉亲和素的四到六步免疫细胞化学技术，在恶性黑色素瘤的福尔马林固定石蜡包埋组织切片上使用抗nm23亲和纯化兔抗人多克隆抗体。我们发现30例CMs中有24例表达nm23，其中10%至50%的黑色素瘤细胞与所用抗体呈现免疫反应性。10例MMCMs均未表达nm23。正如我们在之前的一篇文章中所描述的（48），恶性黑色素瘤的特征是高度的细胞免疫表型异质性。进一步支持这一观察结果的是，我们在构成肿瘤微环境的细胞亚群中观察到了不同水平的nm23染色强度。Nm23/NDP激酶具有多种生物学功能，包括在信号转导和微管组装中的作用。我们认为，nm23/NDP激酶的多种作用主要涉及细胞分裂，这可能是该蛋白水平与转移潜能并未真正相关的潜在原因。因此，nm23蛋白水平可能与增殖率以及肿瘤特异性去分化程度密切相关，而这些是早期诊断、监测肿瘤进展和所采用临床试验疗效以及确定每种肿瘤疾病预后时需要确定的重要参数。
