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Primary and hTERT-Transduced Mesothelioma-Associated Fibroblasts but Not Primary or hTERT-Transduced Mesothelial Cells Stimulate Growth of Human Mesothelioma Cells

Ries, Alexander ; Slany, Astrid ; Pirker, Christine ; Mader, Johanna C. ; Mejri, Doris ; Mohr, Thomas ; Schelch, Karin ; Flehberger, Daniela ; Maach, Nadine and Hashim, Muhammad , et al. (2023) In Cells 12(15).
Abstract

Pleural mesothelioma (PM) is an aggressive malignancy that develops in a unique tumor microenvironment (TME). However, cell models for studying the TME in PM are still limited. Here, we have generated and characterized novel human telomerase reverse transcriptase (hTERT)-transduced mesothelial cell and mesothelioma-associated fibroblast (Meso-CAF) models and investigated their impact on PM cell growth. Pleural mesothelial cells and Meso-CAFs were isolated from tissue of pneumothorax and PM patients, respectively. Stable expression of hTERT was induced by retroviral transduction. Primary and hTERT-transduced cells were compared with respect to doubling times, hTERT expression and activity levels, telomere lengths, proteomes, and the... (More)

Pleural mesothelioma (PM) is an aggressive malignancy that develops in a unique tumor microenvironment (TME). However, cell models for studying the TME in PM are still limited. Here, we have generated and characterized novel human telomerase reverse transcriptase (hTERT)-transduced mesothelial cell and mesothelioma-associated fibroblast (Meso-CAF) models and investigated their impact on PM cell growth. Pleural mesothelial cells and Meso-CAFs were isolated from tissue of pneumothorax and PM patients, respectively. Stable expression of hTERT was induced by retroviral transduction. Primary and hTERT-transduced cells were compared with respect to doubling times, hTERT expression and activity levels, telomere lengths, proteomes, and the impact of conditioned media (CM) on PM cell growth. All transduced derivatives exhibited elevated hTERT expression and activity, and increased mean telomere lengths. Cell morphology remained unchanged, and the proteomes were similar to the corresponding primary cells. Of note, the CM of primary and hTERT-transduced Meso-CAFs stimulated PM cell growth to the same extent, while CM derived from mesothelial cells had no stimulating effect, irrespective of hTERT expression. In conclusion, all new hTERT-transduced cell models closely resemble their primary counterparts and, hence, represent valuable tools to investigate cellular interactions within the TME of PM.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
conditioned medium, hTERT, human telomerase reverse transcriptase, mesothelioma-associated fibroblasts, pleural mesothelial cells, pleural mesothelioma, tumor microenvironment
in
Cells
volume
12
issue
15
article number
2006
publisher
MDPI AG
external identifiers
  • pmid:37566084
  • scopus:85167738920
ISSN
2073-4409
DOI
10.3390/cells12152006
language
English
LU publication?
yes
id
15cdf2c3-fc44-48bc-bd99-10da84bb7126
date added to LUP
2023-10-31 15:07:13
date last changed
2024-04-19 03:14:02
@article{15cdf2c3-fc44-48bc-bd99-10da84bb7126,
  abstract     = {{<p>Pleural mesothelioma (PM) is an aggressive malignancy that develops in a unique tumor microenvironment (TME). However, cell models for studying the TME in PM are still limited. Here, we have generated and characterized novel human telomerase reverse transcriptase (hTERT)-transduced mesothelial cell and mesothelioma-associated fibroblast (Meso-CAF) models and investigated their impact on PM cell growth. Pleural mesothelial cells and Meso-CAFs were isolated from tissue of pneumothorax and PM patients, respectively. Stable expression of hTERT was induced by retroviral transduction. Primary and hTERT-transduced cells were compared with respect to doubling times, hTERT expression and activity levels, telomere lengths, proteomes, and the impact of conditioned media (CM) on PM cell growth. All transduced derivatives exhibited elevated hTERT expression and activity, and increased mean telomere lengths. Cell morphology remained unchanged, and the proteomes were similar to the corresponding primary cells. Of note, the CM of primary and hTERT-transduced Meso-CAFs stimulated PM cell growth to the same extent, while CM derived from mesothelial cells had no stimulating effect, irrespective of hTERT expression. In conclusion, all new hTERT-transduced cell models closely resemble their primary counterparts and, hence, represent valuable tools to investigate cellular interactions within the TME of PM.</p>}},
  author       = {{Ries, Alexander and Slany, Astrid and Pirker, Christine and Mader, Johanna C. and Mejri, Doris and Mohr, Thomas and Schelch, Karin and Flehberger, Daniela and Maach, Nadine and Hashim, Muhammad and Hoda, Mir Alireza and Dome, Balazs and Krupitza, Georg and Berger, Walter and Gerner, Christopher and Holzmann, Klaus and Grusch, Michael}},
  issn         = {{2073-4409}},
  keywords     = {{conditioned medium; hTERT; human telomerase reverse transcriptase; mesothelioma-associated fibroblasts; pleural mesothelial cells; pleural mesothelioma; tumor microenvironment}},
  language     = {{eng}},
  number       = {{15}},
  publisher    = {{MDPI AG}},
  series       = {{Cells}},
  title        = {{Primary and hTERT-Transduced Mesothelioma-Associated Fibroblasts but Not Primary or hTERT-Transduced Mesothelial Cells Stimulate Growth of Human Mesothelioma Cells}},
  url          = {{http://dx.doi.org/10.3390/cells12152006}},
  doi          = {{10.3390/cells12152006}},
  volume       = {{12}},
  year         = {{2023}},
}