Tumor cells derived exosomes contain hTERT mRNA and transform nonmalignant fibroblasts into telomerase positive cells.
Tumor cells derived exosomes contain hTERT mRNA and transform nonmalignant fibroblasts into telomerase positive cells.
复制标题
DOI：
10.18632/oncotarget.10384
复制
发表时间：
2016-09-13
期刊：
影响因子：
--
通讯作者：
Lahav M
中科院分区：
文献类型：
--
作者：
Gutkin A;Uziel O;Beery E;Nordenberg J;Pinchasi M;Goldvaser H;Henick S;Goldberg M;Lahav M
外泌体是一种小的（30-100nm）囊泡，由所有类型的细胞分泌，作为细胞间的通讯工具，并在“受体”细胞摄取后影响其生物过程。目前的研究首次证明，端粒酶的转录本hTERT mRNA通过外泌体从癌细胞穿梭到端粒酶阴性的成纤维细胞，在那里它被翻译成一种完全活跃的酶，并将这些细胞转化为端粒酶阳性，从而创造出一种新型细胞；具有端粒酶活性的非恶性细胞。所有端粒酶阳性细胞，包括端粒酶过表达的癌细胞和非恶性细胞，均根据其内源性hTERT mRNA水平和端粒酶活性分泌外泌体hTERT mRNA。类似地，从胰腺癌和肺癌患者血清中分离的外泌体也含有hTERT mRNA。端粒酶活性诱导受体成纤维细胞的表型变化，包括增殖增加、寿命延长和衰老延缓。此外，端粒酶活性保护成纤维细胞免受静脉霉素诱导的DNA损伤和细胞凋亡，表明端粒酶的“课外”活动也在受体细胞中表现出来。端粒酶从癌细胞向成纤维细胞的穿梭和这种变化的诱导可能有助于癌症微环境的改变及其在癌症中的作用。所描述的过程具有明显的治疗潜力，将在进一步的研究中探索。
Exosomes are small (30-100nm) vesicles secreted from all cell types serving as inter-cell communicators and affecting biological processes in “recipient” cells upon their uptake. The current study demonstrates for the first time that hTERT mRNA, the transcript of the enzyme telomerase, is shuttled from cancer cells via exosomes into telomerase negative fibroblasts, where it is translated into a fully active enzyme and transforms these cells into telomerase positive, thus creating a novel type of cells; non malignant cells with telomerase activity. All tested telomerase positive cells, including cancer cells and non malignant cells with overexpressed telomerase secreted exosomal hTERT mRNA in accordance with the endogenous levels of their hTERT mRNA and telomerase activity. Similarly exosomes isolated from sera of patients with pancreatic and lung cancer contained hTERT mRNA as well. Telomerase activity induced phenotypic changes in the recipient fibroblasts including increased proliferation, extension of life span and postponement of senescence. In addition, telomerase activity protected the fibroblasts from DNA damage induced by phleomycin and from apoptosis, indicating that also telomerase “extracurricular” activities are manifested in the recipient cells. The shuttle of telomerase from cancer cells into fibroblasts and the induction of these changes may contribute to the alterations of cancer microenvironment and its role in cancer. The described process has an obvious therapeutic potential which will be explored in further studies.