Cancer Discov. 2015 Jan 22. pii: CD-14-1022. [Epub ahead of print]

A genetic platform to model sarcomagenesis from primary adult mesenchymal stem cells.

Guarnerio J¹, Riccardi L¹, Taulli R¹, Maeda T², Wang G¹, Hobbs RM¹, Song MS¹, Sportoletti P¹, Bernardi R³, Bronson RT⁴, Castillo-Martin M⁵, Cordon-Cardo C⁵, Lunardi A¹, Pandolfi PP⁶.

Abstract

The regulatory factors governing adult mesenchymal stem cells (MSCs) physiology and their tumorigenic potential are still largely unknown, which substantially delays the identification of effective therapeutic approaches for the treatment of aggressive and lethal form of MSC-derived mesenchymal tumors, such as undifferentiated sarcomas. Here we have developed a novel platform to screen and quickly identify genes and pathways responsible for adult MSCs transformation, modeled undifferentiated sarcoma in vivo, and, ultimately, tested the efficacy of targeting the identified oncopathways. Importantly, by taking advantage of this new platform, we demonstrate the key role of an aberrant LRF- DLK1-SOX9 pathway in the pathogenesis of undifferentiated sarcoma with important therapeutic implications.