Tumor cells derived exosomes contain hTERT mRNA and transform nonmalignant fibroblasts into telomerase positive cells
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Anna Gutkin1,*, Orit Uziel1,2,*, Einat Beery1, Jardena Nordenberg1,2, Maria Pinchasi1,2, Hadar Goldvaser1,3, Steven Henick1, Michal Goldberg4, Meir Lahav1,2,5
1The Felsenstein Medical Research Center, Rabin Medical Center, Petah Tikva, Israel
2Sackler School of Medicine, Tel-Aviv University, Petah Tikva, Israel
3Institute of Oncology, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel
4Department of Genetics, Institute of Life Sciences, Hebrew University of Jerusalem, Petah Tikva, Israel
5Institute of Hematology, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel
*These authors have contributed equally to this work
Meir Lahav, email: [email protected]
Keywords: exosomes, telomerase
Received: March 27, 2016 Accepted: June 06, 2016 Published: July 02, 2016
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.
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