Mandic R, Dünne A A, Eikelkamp N, Ramaswamy A, Schulz S, Teymoortash A, Sesterhenn A, Moll R, Werner J A
Department of Otorhinolaryngology, Philipps University, Deutschhausstr. 3, 35037 Marburg, Germany.
Anticancer Res. 2002 Nov-Dec;22(6A):3281-4.
Squamous cell carcinomas of the head and neck region (HNSCC) are among the most common malignancies in this area. The VX2 carcinoma of the New Zealand white rabbit metastasizes lymphatically as is the case in HNSCC and therefore, potentially, could be used as a model for HNSCC. Since the family of matrix-metalloproteinases (MMPs) is involved in the process of HNSCC invasion, the aim of this study was to investigate the expression level of MMPs and their specific inhibitors (TIMPs) in the VX2 carcinoma to evaluate if they also play a role in VX2 tumor invasion as observed in human HNSCC.
The VX2 carcinoma was generated by tumor implantation in the rabbit's ear as previously described. Western blots were performed under standard conditions, utilizing antibodies against MMP-3, MMP-13, TIMP-2 and TIMP-3. Immunohistochemical staining was performed with the ABC-complex method.
A positive immunohistochemical signal could be detected for MMP-3, TIMP-2 and TIMP-3 with no significant signal for MMP-13. In the Western blots immunoreactive bands could be observed for MMP-3, MMP-13, TIMP-2 and TIMP-3.
MMP-3, MMP-13, TIMP-2 and TIMP-3 were found to be expressed in VX2 carcinomas of the New Zealand white rabbits. The VX2 carcinoma therefore resembles HNSCC tumors not only in its metastatic behavior, but also regarding the expression of MMPs and TIMPs, which are the probable keyplayers during the event of invasion. These observations further underline the significance of the VX2 carcinoma as a model tumor of human HNSCC.
头颈部鳞状细胞癌(HNSCC)是该区域最常见的恶性肿瘤之一。新西兰白兔的VX2癌会发生淋巴转移,这与HNSCC的情况相同,因此有可能用作HNSCC的模型。由于基质金属蛋白酶(MMPs)家族参与了HNSCC的侵袭过程,本研究的目的是调查VX2癌中MMPs及其特异性抑制剂(TIMPs)的表达水平,以评估它们是否也在VX2肿瘤侵袭中发挥作用,就像在人类HNSCC中观察到的那样。
如前所述,通过在兔耳中植入肿瘤来生成VX2癌。在标准条件下进行蛋白质免疫印迹,使用针对MMP-3、MMP-13、TIMP-2和TIMP-3的抗体。采用ABC复合方法进行免疫组织化学染色。
MMP-3、TIMP-2和TIMP-3可检测到阳性免疫组织化学信号,而MMP-13无明显信号。在蛋白质免疫印迹中,可观察到MMP-3、MMP-13、TIMP-2和TIMP-3的免疫反应条带。
发现MMP-3、MMP-13、TIMP-2和TIMP-3在新西兰白兔的VX2癌中表达。因此,VX2癌不仅在转移行为上与HNSCC肿瘤相似,而且在MMPs和TIMPs的表达方面也相似,而这些可能是侵袭过程中的关键因素。这些观察结果进一步强调了VX2癌作为人类HNSCC模型肿瘤的重要性。