Meyer A, Gruber A D, Klopfleisch R
Department of Veterinary Pathology, Freie Universität Berlin, Robert-von-Ostertag-Straße 15, 14163 Berlin, Germany.
J Comp Pathol. 2013 Jul;149(1):19-29. doi: 10.1016/j.jcpa.2012.11.232. Epub 2012 Dec 28.
Cutaneous mast cell tumours (MCTs) are among the most important skin tumours in dogs. Apart from c-KIT mutations, which are present in <18% of MCTs, little is known of the mechanisms of MCT development and independent growth of tumour cells. Recently, the α-subunit (CD25) of the interleukin (IL)-2 receptor (IL-2R) has been found to be expressed by canine cutaneous MCTs and this expression is negatively correlated with tumour grade. We thus hypothesized that the other two subunits of the IL-2R and the ligand IL-2 are also expressed and that IL-2-dependent pathways may have an impact on MCT development and independent tumour cell growth. Messenger RNA and protein expression levels of the IL-2R β-subunit (CD122), the IL-2R γ-subunit (CD132) and IL-2 were analyzed in canine cutaneous MCTs and compared with tumour grade and c-KIT mutation status. Eighty-six percent of the tumours expressed both subunits of the IL-2R and 64% expressed IL-2. In addition, neoplastic mast cells seem able to bind IL-2. IL-2Rγ and IL-2 protein expression levels were significantly decreased in higher grade tumours and IL-2 expression was significantly decreased in c-KIT mutated tumours. Thus, expression of the complete IL-2R and its ligand by canine cutaneous MCTs indicates a potential impact of IL-2R signalling in MCT development and tumour cell proliferation. The decrease in IL-2R expression with increasing histological evidence of malignancy suggests that the IL-2R may be more relevant for early MCT development and well-differentiated tumours.
皮肤肥大细胞瘤(MCTs)是犬类最重要的皮肤肿瘤之一。除了c-KIT突变(存在于不到18%的MCTs中)外,人们对MCTs的发生机制以及肿瘤细胞的自主生长知之甚少。最近,发现白细胞介素(IL)-2受体(IL-2R)的α亚基(CD25)在犬皮肤MCTs中表达,且这种表达与肿瘤分级呈负相关。因此,我们推测IL-2R的其他两个亚基以及配体IL-2也有表达,并且IL-2依赖途径可能对MCTs的发生和肿瘤细胞的自主生长有影响。对犬皮肤MCTs中IL-2Rβ亚基(CD122)、IL-2Rγ亚基(CD132)和IL-2的信使核糖核酸和蛋白质表达水平进行了分析,并与肿瘤分级和c-KIT突变状态进行了比较。86%的肿瘤表达了IL-2R的两个亚基,64%表达了IL-2。此外,肿瘤性肥大细胞似乎能够结合IL-2。在高级别肿瘤中,IL-2Rγ和IL-2蛋白表达水平显著降低,在c-KIT突变的肿瘤中IL-2表达显著降低。因此,犬皮肤MCTs中完整IL-2R及其配体的表达表明IL-2R信号传导在MCTs发生和肿瘤细胞增殖中具有潜在影响。随着恶性组织学证据增加,IL-2R表达降低,这表明IL-2R可能与早期MCTs发生和高分化肿瘤更相关。