Falchetti Maria Laura, Pierconti Francesco, Casalbore Patrizia, Maggiano Nicola, Levi Andrea, Larocca Luigi Maria, Pallini Roberto
Institute of Neurobiology and Molecular Medicine, Consiglio Nazionale delle Ricerche, Rome 00137, Italy.
Cancer Res. 2003 Jul 1;63(13):3750-4.
Angiogenesis is essential for the growth of solid tumors. We have observed previously that the vascular endothelial cells of astrocytic brain tumors express human telomerase reverse transcriptase (hTERT) mRNA, suggesting a role for telomerase in the angiogenesis of these neoplasms. Here, we used an in vitro model to demonstrate that the telomerase machinery might be trans-activated in primary endothelial cells by glioblastoma tumor cells. We found that glioblastoma cells in vitro do induce hTERT mRNA and hTERT protein expression, as well as telomerase enzyme activity in the endothelial cells, and that this phenomenon is mediated by diffusible factor(s). These results provide strong evidence of the involvement of telomerase in tumor angiogenesis and will stimulate research on antitelomerase drugs for treatment of malignant brain gliomas.
血管生成对于实体瘤的生长至关重要。我们之前观察到,星形细胞瘤脑肿瘤的血管内皮细胞表达人端粒酶逆转录酶(hTERT)mRNA,这表明端粒酶在这些肿瘤的血管生成中发挥作用。在此,我们使用体外模型证明,胶质母细胞瘤肿瘤细胞可能在原代内皮细胞中反式激活端粒酶机制。我们发现,体外的胶质母细胞瘤细胞确实能诱导内皮细胞中hTERT mRNA和hTERT蛋白表达以及端粒酶活性,并且这种现象是由可扩散因子介导的。这些结果为端粒酶参与肿瘤血管生成提供了有力证据,并将推动针对抗端粒酶药物治疗恶性脑胶质瘤的研究。