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Research Article
Orit Uziel
The Felsenstein Medical Research Center
Corresponding Author
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It is now well accepted that cancer cells change their microenvironment from normal to tumor-supportive state to provide sustained tumor growth, metastasis and drug resistance. These processes are partially carried out by exosomes, nano-sized vesicles secreted from cells, shuttled from donor to recipient cells containing a cargo of nucleic acids, proteins and lipids. By transferring biologically active molecules, cancer-derived exosomes may educate microenvironmental cells to become tumor supportive. We have recently shown that the transcript of human telomerase reverse transcriptase (hTERT), the hallmark of cancer cells is packaged in cancer cells derived- exosomes. After the engulfment of the hTERT transcript into fibroblasts, it is translated into a fully active enzyme. Telomerase activity in the recipient, otherwise telomerase negative cells, provides them with a survival advantage. Here we show that exosomal telomerase plays a role in modifying normal fibroblasts into cancer associated fibroblasts (CAFs) by upregulating aSMA and Vimentin, two CAF markers. We also show that telomerase activity changes the transcriptome of microRNA in these fibroblasts. By ectopically expressing microRNA 342, one of the top identified microRNAs we show that it may mediate the proliferative phenotype that these cells acquire upon taking-up exosomal hTERT, providing them with a survival advantage.
Keywords
Human telomerase reverse transcriptase (hTERT), exosomes, microRNA, tumor microenvironment, cancer
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No competing interests reported.
This is a list of supplementary files associated with this preprint. Click to download.
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This preprint is under consideration at Scientific Reports. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research Article
Orit Uziel
The Felsenstein Medical Research Center
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 16 Nov, 2021
No community comments so far
Editor invited
On 12 Nov, 2021
Submission checks complete
On 12 Nov, 2021
First submitted
On 28 Oct, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
It is now well accepted that cancer cells change their microenvironment from normal to tumor-supportive state to provide sustained tumor growth, metastasis and drug resistance. These processes are partially carried out by exosomes, nano-sized vesicles secreted from cells, shuttled from donor to recipient cells containing a cargo of nucleic acids, proteins and lipids. By transferring biologically active molecules, cancer-derived exosomes may educate microenvironmental cells to become tumor supportive. We have recently shown that the transcript of human telomerase reverse transcriptase (hTERT), the hallmark of cancer cells is packaged in cancer cells derived- exosomes. After the engulfment of the hTERT transcript into fibroblasts, it is translated into a fully active enzyme. Telomerase activity in the recipient, otherwise telomerase negative cells, provides them with a survival advantage. Here we show that exosomal telomerase plays a role in modifying normal fibroblasts into cancer associated fibroblasts (CAFs) by upregulating aSMA and Vimentin, two CAF markers. We also show that telomerase activity changes the transcriptome of microRNA in these fibroblasts. By ectopically expressing microRNA 342, one of the top identified microRNAs we show that it may mediate the proliferative phenotype that these cells acquire upon taking-up exosomal hTERT, providing them with a survival advantage.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
No competing interests reported.
This is a list of supplementary files associated with this preprint. Click to download.
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