Transcriptome analysis of tumor-derived mesenchymal progenitor cells shows that is a fibrosis regulator of retroperitoneal liposarcoma.

Background: Retroperitoneal liposarcoma (RPLS) is a rare, biologically heterogeneous tumor with distinct clinical characteristics, such as frequent local recurrence, repeated relapse, and rare distant metastasis. No effective targeted therapy is available for RPLS. Here, we aim to determine the pathological functions and therapeutic potential of carbohydrate sulfotransferase 15 () in RPLS.

Methods: Tumor-derived mesenchymal progenitor cells (MPCs) and normal adipose derived mesenchymal stem cells (MSCs) were obtained from patients with RPLS. MPCs and MSCs were isolated and characterized based on surface markers, proliferation, and differentiation using flow cytometry and molecular staining. Transcriptome analysis was performed to decipher expression profile of differentiation-related genes in 3 paired MSCs and MPCs. Further confirmation of genes were performed using quantitative real-time polymerase chain reaction (qRT-PCR). Plasmids overexpressing were transfected into adipose MSCs to examine fibrosis-related gene expression at mRNA level by real-time PCR.

Results: The tumor stromal-derived MPCs expressed CD105, CD73, and CD90, and exhibited osteogenic and adipogenic differentiation potential . The proliferation of tumor-derived MPCs was significantly lower than that of normal adipose-derived MSCs (P<0.001). Transcriptome analysis revealed upregulation of , , , and in tumor-derived MPCs. was highly expressed in tumor-derived MPCs (P<0.001). mediated fibrosis-related gene expression in MSCs (P<0.05) and MPCs (P<0.001).

Conclusions: is upregulated in tumor-derived MPCs and regulates fibrosis in RPLS. This provides clues for development of novel therapeutic strategies by targeting -induced MPC activation in RPLS.