Lucia Casadei, Federica Calore, Danielle A Braggio, Abeba Zewdu, Ameya A Deshmukh, Paolo Fadda, Gonzalo Lopez, Martin Wabitsch, Chi Song, Jennifer L Leight, Valerie P Grignol, Dina Lev, Carlo M Croce, Raphael E Pollock
Dedifferentiated liposarcoma (DDLPS) is frequently diagnosed late, and patients typically respond poorly to treatments. DDLPS is molecularly characterized by wild-type p53 and amplification of the MDM2 gene, which results in overexpression of MDM2 protein, a key oncogenic process in DDLPS. In this study, we demonstrate that extracellular vesicles derived from patients with DDLPS or from DDLPS cell lines are carriers of MDM2 DNA that can be transferred to preadipocytes, a major and ubiquitous cellular component of the DDLPS tumor microenvironment, leading to impaired p53 activity in preadipocytes and increased proliferation, migration, and production of matrix metalloproteinase 2; treatment with MDM2 inhibitors repressed these effects...
October 1, 2019: Cancer Research