Exosome-Derived miR-25-3p and miR-92a-3p Stimulate Liposarcoma Progression.

Casadei L1,2, Calore F3, Creighton CJ4, Guescini M5, Batte K1,2, Iwenofu OH6, Zewdu A1,2, Braggio DA1,2, Bill KL1,2, Fadda P3, Lovat F3, Lopez G1,2, Gasparini P3, Chen JL1,2, Kladney RD3,7,8, Leone G3,7,8, Lev D9, Croce CM10, Pollock RE11,2
Source: Cancer Res
Publication Date: ()
Issue: 77: 3846-3856
Cells used in publication:
Adipocyte (pre), human
Species: human
Tissue Origin: adipose


Despite the development of combined modality treatments against liposarcoma in recent years, a significant proportion of patients respond only modestly to such approaches, possibly contributing to local or distant recurrence. Early detection of recurrent or metastatic disease could improve patient prognosis by triggering earlier clinical intervention. However, useful biomarkers for such purposes are lacking. Using both patient plasma samples and cell lines, we demonstrate here that miR-25-3p and miR-92a-3p are secreted by liposarcoma cells through extracellular vesicles and may be useful as potential biomarkers of disease. Both miR-25-3p and miR-92a-3p stimulated secretion of proinflammatory cytokine IL6 from tumor-associated macrophages in a TLR7/8-dependent manner, which in turn promoted liposarcoma cell proliferation, invasion, and metastasis via this interaction with the surrounding microenvironment. Our findings provide novel and previously unreported insight into liposarcoma progression, identifying communication between liposarcoma cells and their microenvironment as a process critically involved in liposarcoma progression. This study establishes the possibility that the pattern of circulating miRNAs may identify recurrence prior to radiological detectability while providing insight into disease outcome and as a possible approach to monitor treatment efficacy.