Abstract:
Human inflammatory breast cancer (IBC) and canine inflammatory mammary cancer (IMC) are the most aggressive and lethal types of mammary tumors with specific characteristics such as exacerbated angiogenesis, lymphangiogenesis and lymphangiotropism. E-cadherin expression is another specific feature of IBC not previously studied in canine IMC. In this study, the expression of E-cadherin and CADM1 (Cell Adhesion molecule 1) and their possible role as key molecules involved in the pathogenesis of IMC were immunohistochemically analyzed in 19 canine IMC and 15 grade III non-IMC cases. E-cadherin and CADM1 expression was higher in IMC cases (p = 0.002, p = 0.008, respectively). In the IMC group, E-cadherin cytoplasmic immunolabeling was more frequent (p = 0.035) and it was associated to the expression of the angiogenic and lymphangiogenic factors COX-2 (p = 0.009), VEGF-A (p = 0.031) and VEGF-D (p = 0.008). The differential mRNA expression between IMC and non-IMC was studied by microarray analysis in 6 cases. E-cadherin gene (CDH1) was not up-regulated in IMC cases at a transcriptional level; interestingly CADM1 was 7-fold upregulated. The differential expression of E-cadherin protein in IMC suggests a possible role of E-cadherin in the characteristic exacerbated angiogenesis and lymphangiogenesis and further support IMC as a natural model for the study of human IBC. Future studies in IBC and IMC including a broad panel of adhesion molecules are necessary to elucidate their role in the metastatic process and angiogenesis.
摘要:
人类炎性乳腺癌(IBC)和犬炎性乳腺癌(IMC)是最具侵袭性和致死性的乳腺肿瘤类型,具有血管生成加剧等特定特征,淋巴管生成和淋巴管生成。E-钙黏着蛋白的表达是IBC的另一个特定特征,以前没有在犬IMC中研究过。在这项研究中,对19例犬IMC和15例III级非IMC病例中E-cadherin和CADM1(细胞粘附分子1)的表达及其作为IMC发病关键分子的可能作用进行了免疫组织化学分析。E-cadherin和CADM1在IMC病例中表达较高(分别为p=0.002,p=0.008)。在IMC组中,E-cadherin细胞质免疫标记更频繁(p=0.035),它与血管生成和淋巴管生成因子COX-2的表达有关(p=0.009),VEGF-A(p=0.031)和VEGF-D(p=0.008)。通过微阵列分析研究了6例IMC与非IMC之间的差异mRNA表达。在IMC病例中,E-cadherin基因(CDH1)在转录水平上没有上调;有趣的是,CADM1上调了7倍。E-cadherin蛋白在IMC中的差异表达表明E-cadherin在特征性加剧的血管生成和淋巴管生成中可能发挥作用,并进一步支持IMC作为人类IBC研究的自然模型。IBC和IMC的未来研究包括一组广泛的粘附分子对于阐明它们在转移过程和血管生成中的作用是必要的。