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2016 ; 7
(37
): 59173-59188
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Tumor cells derived exosomes contain hTERT mRNA and transform nonmalignant
fibroblasts into telomerase positive cells
#MMPMID27385095
Gutkin A
; Uziel O
; Beery E
; Nordenberg J
; Pinchasi M
; Goldvaser H
; Henick S
; Goldberg M
; Lahav M
Oncotarget
2016[Sep]; 7
(37
): 59173-59188
PMID27385095
show ga
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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