Mukaratirwa S, Chimonyo M, Obwolo M, Gruys E, Nederbragt H
Department of Pathobiology, Utrecht University.
Histol Histopathol. 2004 Oct;19(4):1117-23. doi: 10.14670/HH-19.1117.
Stromal cells and extracellular matrix (ECM) components are important for tumour cell behaviour. Little is known about the role of stromal cells and ECM components in the progression and regression of spontaneous canine transmissible venereal tumour (CTVT). In this study, the stromal cell type was determined by immunohistochemical labelling with antibodies to desmin, vimentin and alpha-smooth muscle actin (alpha-SMA) during the progressive and regressive stages of spontaneous CTVT. The distribution of ECM components tenascin-C, chondroitin sulphate and versican were determined immunohistochemically, and hyaluronan distribution was determined using a biotinylated protein complex with specific affinity for hyaluronan. Stromal cells of tumours in both the progressive and regressive stage were positive for vimentin and negative for desmin. The number of stromal cells expressing alpha-SMA was significantly higher (P=0.001) in regressing tumours, than progressing tumours. These results suggest that the modulation of stromal cells that occurs during the regression of CTVT is similar to that occurring during wound healing. Tenascin-C was weakly expressed in the stroma of tumours in the progressive stage and in regions of the regressing tumours with tumour infiltrating lymphocytes (TILs), but intensely expressed in the stroma of tumours in late regressive stage. In addition, tenascin-C was also expressed in the cytoplasm of some tumour cells in the late regressive stage. A strong stromal tenascin-C intensity was significantly associated with regressing tumours (P=0.001). Strong stromal hyaluronan intensity and a high proportion of hyaluronan-positive tumour cells were significantly associated with progressing tumours (P=0.001). This suggests that hyaluronan is involved in the growth of the tumour. There was no significant difference in the expression of chondroitin sulphate and versican in progressing and regressing tumours.
基质细胞和细胞外基质(ECM)成分对肿瘤细胞行为很重要。关于基质细胞和ECM成分在自发性犬传染性性病肿瘤(CTVT)进展和消退中的作用知之甚少。在本研究中,通过用抗结蛋白、波形蛋白和α-平滑肌肌动蛋白(α-SMA)抗体进行免疫组织化学标记,确定了自发性CTVT进展期和消退期的基质细胞类型。免疫组织化学法测定了细胞外基质成分肌腱蛋白-C、硫酸软骨素和多功能蛋白聚糖的分布,并用对透明质酸具有特异性亲和力的生物素化蛋白复合物测定了透明质酸的分布。进展期和消退期肿瘤的基质细胞波形蛋白呈阳性,结蛋白呈阴性。消退期肿瘤中表达α-SMA的基质细胞数量显著高于进展期肿瘤(P=0.001)。这些结果表明,CTVT消退过程中发生的基质细胞调节与伤口愈合过程中发生的调节相似。肌腱蛋白-C在进展期肿瘤的基质以及有肿瘤浸润淋巴细胞(TILs)的消退期肿瘤区域中弱表达,但在消退后期肿瘤的基质中强烈表达。此外,在消退后期,一些肿瘤细胞的细胞质中也表达肌腱蛋白-C。基质肌腱蛋白-C的高强度与消退期肿瘤显著相关(P=0.001)。基质透明质酸高强度和高比例的透明质酸阳性肿瘤细胞与进展期肿瘤显著相关(P=0.001)。这表明透明质酸参与肿瘤生长。进展期和消退期肿瘤中硫酸软骨素和多功能蛋白聚糖的表达无显著差异。