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Tetraploidization Increases the Motility and Invasiveness of Cancer Cells

Jemaà, Mohamed LU ; Daams, Renee LU ; Charfi, Slim ; Mertens, Fredrik LU ; Huber, Stephan M. and Massoumi, Ramin LU (2023) In International Journal of Molecular Sciences 24(18).
Abstract

Polyploidy and metastasis are associated with a low probability of disease-free survival in cancer patients. Polyploid cells are known to facilitate tumorigenesis. However, few data associate polyploidization with metastasis. Here, by generating and using diploid (2n) and tetraploid (4n) clones from malignant fibrous histiocytoma (MFH) and colon carcinoma (RKO), we demonstrate the migration and invasion advantage of tetraploid cells in vitro using several assays, including the wound healing, the OrisTM two-dimensional cell migration, single-cell migration tracking by video microscopy, the Boyden chamber, and the xCELLigence RTCA real-time cell migration. Motility advantage was observed despite tetraploid cell proliferation weakness. We... (More)

Polyploidy and metastasis are associated with a low probability of disease-free survival in cancer patients. Polyploid cells are known to facilitate tumorigenesis. However, few data associate polyploidization with metastasis. Here, by generating and using diploid (2n) and tetraploid (4n) clones from malignant fibrous histiocytoma (MFH) and colon carcinoma (RKO), we demonstrate the migration and invasion advantage of tetraploid cells in vitro using several assays, including the wound healing, the OrisTM two-dimensional cell migration, single-cell migration tracking by video microscopy, the Boyden chamber, and the xCELLigence RTCA real-time cell migration. Motility advantage was observed despite tetraploid cell proliferation weakness. We could also demonstrate preferential metastatic potential in vivo for the tetraploid clone using the tail vein injection in mice and tracking metastatic tumors in the lung. Using the Mitelman Database of Chromosome Aberrations in Cancer, we found an accumulation of polyploid karyotypes in metastatic tumors compared to primary ones. This work reveals the clinical relevance of the polyploid subpopulation and the strategic need to highlight polyploidy in preclinical studies as a therapeutic target for metastasis.

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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
colon cancer, invasion, metastasis, migration, sarcoma, tetraploidy
in
International Journal of Molecular Sciences
volume
24
issue
18
article number
13926
publisher
MDPI AG
external identifiers
  • pmid:37762227
  • scopus:85172872780
ISSN
1661-6596
DOI
10.3390/ijms241813926
language
English
LU publication?
yes
id
f72b8801-5a0f-4442-aa19-0ede13c02d03
date added to LUP
2023-12-18 09:24:40
date last changed
2024-04-16 21:36:31
@article{f72b8801-5a0f-4442-aa19-0ede13c02d03,
  abstract     = {{<p>Polyploidy and metastasis are associated with a low probability of disease-free survival in cancer patients. Polyploid cells are known to facilitate tumorigenesis. However, few data associate polyploidization with metastasis. Here, by generating and using diploid (2n) and tetraploid (4n) clones from malignant fibrous histiocytoma (MFH) and colon carcinoma (RKO), we demonstrate the migration and invasion advantage of tetraploid cells in vitro using several assays, including the wound healing, the OrisTM two-dimensional cell migration, single-cell migration tracking by video microscopy, the Boyden chamber, and the xCELLigence RTCA real-time cell migration. Motility advantage was observed despite tetraploid cell proliferation weakness. We could also demonstrate preferential metastatic potential in vivo for the tetraploid clone using the tail vein injection in mice and tracking metastatic tumors in the lung. Using the Mitelman Database of Chromosome Aberrations in Cancer, we found an accumulation of polyploid karyotypes in metastatic tumors compared to primary ones. This work reveals the clinical relevance of the polyploid subpopulation and the strategic need to highlight polyploidy in preclinical studies as a therapeutic target for metastasis.</p>}},
  author       = {{Jemaà, Mohamed and Daams, Renee and Charfi, Slim and Mertens, Fredrik and Huber, Stephan M. and Massoumi, Ramin}},
  issn         = {{1661-6596}},
  keywords     = {{colon cancer; invasion; metastasis; migration; sarcoma; tetraploidy}},
  language     = {{eng}},
  number       = {{18}},
  publisher    = {{MDPI AG}},
  series       = {{International Journal of Molecular Sciences}},
  title        = {{Tetraploidization Increases the Motility and Invasiveness of Cancer Cells}},
  url          = {{http://dx.doi.org/10.3390/ijms241813926}},
  doi          = {{10.3390/ijms241813926}},
  volume       = {{24}},
  year         = {{2023}},
}