Abstract
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.
Highlights
Telomerase, a unique reverse transcriptase maintains telomere length by synthesizing TTAGGG repeats at their ends [1]
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, creating a novel type of cells; non malignant cells with telomerase activity
The relative telomerase activity and hTERT expression were demonstrated in the following cells: Jurkat (T cell leukemia), MCF-7, K562 and HCT116; pHFF and pHFF-Tel cells transfected with the hTERT gene
Summary
Telomerase, a unique reverse transcriptase maintains telomere length by synthesizing TTAGGG repeats at their ends [1]. In humans telomerase is transcriptionally repressed at birth and remains inactive through life in most somatic cells. Telomerase activity prevents cellular replicative senescence and confers longevity or even immortality to the cell. It has several cellular functions, some of them are telomere related and some, e.g. prevention of apoptosis and others are independent of telomere length maintenance and termed “extracurricular” activities of telomerase [2]. Telomerase repression in human somatic cells is a major cause of senescence, aging and as such is considered a cancer suppressive mechanism. Telomerase is activated in >90% of cancer cells and considered a hallmark of cancer. Several recent studies so far demonstrated that transcripts of telomerase (hTERT, human telomerase reverse transcriptase) can be www.impactjournals.com/oncotarget detected in the serum of cancer patients in breast, colon, hepatocellular carcinoma and follicular lymphoma([4 and references therein)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
