Polyploidization of murine mesenchymal cells is associated with suppression of the long noncoding RNA H19 and reduced tumorigenicity

Mesenchymal stromal cells (MSC) are used extensively in clinical trials; however, the possibility that MSCs have a potential for malignant transformation was raised. We examined the genomic stability versus the tumor-forming capacity of multiple mouse MSCs. Murine MSCs have been shown to be less sta...

Full description

Saved in:
Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2012-12, Vol.72 (24), p.6403-6413
Main Authors: Shoshani, Ofer, Massalha, Hassan, Shani, Nir, Kagan, Sivan, Ravid, Orly, Madar, Shalom, Trakhtenbrot, Luba, Leshkowitz, Dena, Rechavi, Gideon, Zipori, Dov
Format: Article
Language:English
Subjects:
Animals
Cell Transformation, Neoplastic - genetics
Cell Transformation, Neoplastic - pathology
Cells, Cultured
Gene Silencing - physiology
Genomic Instability
Mesenchymal Stromal Cells - metabolism
Mesenchymal Stromal Cells - pathology
Mesenchymal Stromal Cells - physiology
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Inbred NOD
Mice, Knockout
Mice, SCID
Neoplasms - genetics
Polyploidy
RNA, Long Noncoding - antagonists & inhibitors
RNA, Long Noncoding - genetics
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Mesenchymal stromal cells (MSC) are used extensively in clinical trials; however, the possibility that MSCs have a potential for malignant transformation was raised. We examined the genomic stability versus the tumor-forming capacity of multiple mouse MSCs. Murine MSCs have been shown to be less stable and more prone to malignant transformation than their human counterparts. A large series of independently isolated MSC populations exhibited low tumorigenic potential under syngeneic conditions, which increased in immunocompromised animals. Unexpectedly, higher ploidy correlated with reduced tumor-forming capacity. Furthermore, in both cultured MSCs and primary hepatocytes, polyploidization was associated with a dramatic decrease in the expression of the long noncoding RNA H19. Direct knockdown of H19 expression in diploid cells resulted in acquisition of polyploid cell traits. Moreover, artificial tetraploidization of diploid cancer cells led to a reduction of H19 levels, as well as to an attenuation of the tumorigenic potential. Polyploidy might therefore serve as a protective mechanism aimed at reducing malignant transformation through the involvement of the H19 regulatory long noncoding RNA.
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.CAN-12-1155