Zafiropoulos Alexandros, Nikitovic Dragana, Katonis Pavlos, Tsatsakis Aristidis, Karamanos Nikos K, Tzanakakis George N
Department of Histology, Division of Morphology, School of Medicine, University of Crete, 71110 Heraklion, Greece.
Mol Cancer Res. 2008 May;6(5):785-94. doi: 10.1158/1541-7786.MCR-07-0165.
Decorin is an established natural oncosuppressive factor whose action is being studied in detail. Recently, decorin gene therapy formulations using adenoviral vectors have been shown in several animal models with very promising results. The present study describes the first exception to the established oncosuppression model using human osteosarcoma cells. MG-63 osteosarcoma cells were found to constitutively produce decorin, and furthermore, to be resistant to decorin-induced growth arrest. On the contrary, decorin seemed to be beneficial to osteosarcoma cells because it was necessary for MG-63 cell migration and acted as a mediator, counteracting the transforming growth factor-beta2-induced cytostatic function. Efforts to determine how MG-63 cells could overcome the decorin-induced cytostatic effect established that decorin in MG-63 cells does not induce p21 expression nor does it cause protracted retraction and inactivation of the epidermal growth factor receptor. Conversely, epidermal growth factor receptor seemed to be overexpressed and continuously phosphorylated. In view of the proposed design of decorin-based anticancer therapeutic strategies, our study provides new data on pathways that cancer cells might employ to overcome the established decorin-induced growth suppression.
核心蛋白聚糖是一种已确定的天然肿瘤抑制因子，其作用正在被详细研究。最近，使用腺病毒载体的核心蛋白聚糖基因治疗制剂在多种动物模型中显示出非常有前景的结果。本研究描述了使用人骨肉瘤细胞对既定肿瘤抑制模型的首个例外情况。发现MG-63骨肉瘤细胞组成性地产生核心蛋白聚糖，而且对核心蛋白聚糖诱导的生长停滞具有抗性。相反，核心蛋白聚糖似乎对骨肉瘤细胞有益，因为它对MG-63细胞迁移是必需的，并且作为一种介质，抵消转化生长因子-β2诱导的细胞生长抑制功能。确定MG-63细胞如何克服核心蛋白聚糖诱导的细胞生长抑制作用的研究表明，MG-63细胞中的核心蛋白聚糖既不诱导p21表达，也不会导致表皮生长因子受体的长期回缩和失活。相反，表皮生长因子受体似乎过度表达并持续磷酸化。鉴于基于核心蛋白聚糖的抗癌治疗策略的设计，我们的研究提供了关于癌细胞可能用于克服既定的核心蛋白聚糖诱导的生长抑制的途径的新数据。
