Genome remodeling upon mesenchymal tumor cell fusion contributes to tumor progression and metastatic spread.
Oncogene
; 39(21): 4198-4211, 2020 05.
Article
em En
| MEDLINE
| ID: mdl-32242148
ABSTRACT
Cell fusion in tumor progression mostly refers to the merging of a cancer cell with a cell that has migration and immune escape capabilities such as macrophages. Here we show that spontaneous hybrids made from the fusion of transformed mesenchymal cells with partners from the same lineage undergo nonrecurrent large-scale genomic rearrangements, leading to the creation of highly aneuploid cells with novel phenotypic traits, including metastatic spreading capabilities. Moreover, in contrast to their parents, hybrids were the only cells able to recapitulate in vivo all features of human pleomorphic sarcomas, a rare and genetically complex mesenchymal tumor. Hybrid tumors not only displayed specific mesenchymal markers, but also combined a complex genetic profile with a highly metastatic behavior, like their human counterparts. Finally, we provide evidence that patient-derived pleomorphic sarcoma cells are inclined to spontaneous cell fusion. The resulting hybrids also gain in aggressiveness, exhibiting superior growth capacity in mouse models. Altogether, these results indicate that cell fusion has the potential to promote cancer progression by increasing growth and/or metastatic capacities, regardless of the nature of the companion cell. Moreover, such events likely occur upon sarcoma development, paving the way for better understanding of the biology, and aggressiveness of these tumors.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sarcoma
/
Células-Tronco Neoplásicas
/
Genoma Humano
/
Transição Epitelial-Mesenquimal
/
Células-Tronco Mesenquimais
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Oncogene
Assunto da revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
França