RT Journal Article
SR Electronic
T1 An evolving cancer instigates clonally unrelated neighboring cells to form distant metastases
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 085423
DO 10.1101/085423
A1 Jie Dong
A1 Cedric Darini
A1 Farhia Kabeer
A1 Sarah Dendievel
A1 Junxia Min
A1 Dolores Hambardzumyan
A1 Louis Gaboury
A1 Tom Lenaerts
A1 Guillaume Darrasse-Jèze
A1 Yi Li
A1 Katrina Podsypanina
YR 2016
UL http://biorxiv.org/content/early/2016/11/03/085423.abstract
AB Based on the clonal evolution theory of cancer formation, a single cell within a tissue gains a cancer-driving mutation and thus a growth advantage. From this expanded cellular mass, another cell gains a new mutation allowing this newly mutated cell to gain new competitive advantage and to expand in number (thus clonal expansion). Another clone then emerges. Eventually all required mutations are gained, and a cancer forms. Consequently, while a primary lesion may harbor divergent subclones, all the subclones within the primary cancer as well as all metastatic growths in secondary organs share at least the very first oncogenic mutation that initiates the primary cancer. However, by tracking genetically marked mammary epithelial cells that suffered the initiating oncogenic mutation—and their neighboring mammary cells that did not-in several mouse models of human breast cancer, we found that genetically unrelated mammary epithelial cells can be colluded by neighboring mutated cells to disseminate, and that they can even undergo de novo tumorigenic transformation and form distant metastases. Therefore, clonally unrelated epithelial cells may contribute to cancer progression and to the heterogeneity of the systemic disease. The non-linear cancer spread has important implications in cancer prevention, treatment, and therapeutic resistance.