DDIT3 Expression in Liposarcoma Development.
Liposarcomas are mesenchymal tumors containing variable numbers of lipoblasts or adipocytes. The most common entities, well differentiated/dedifferentiated liposarcoma (WDLS/DDLS) and myxoid/round cell liposarcoma (MLS/RCLS), are both characterized by genetic rearrangements that affect the expression of the transcription factor DDIT3. DDIT3 induces liposarcoma morphology when ectopically expressed in a human fibrosarcoma. The role of DDIT3 in lipomatous tumors is, however, unclear. We have analyzed the expression of DDIT3 in 37 cases of liposarcoma (WDLS/DDLS n = 10, MLS/RCLS n = 16, and pleomorphic liposarcomas (PLS) n = 11) and 11 cases of common benign lipomas. Major cell subpopulations of WDLS/DDLS and MLS/RCLS tumors were found to express DDIT3 or the derived fusion protein, whereas PLS cases showed only a few positive cells. The lipomas contained large subpopulations expressing DDIT3. No correlation between numbers of DDIT3 expressing cells and numbers of lipoblasts/adipocytes was found. In vitro adipogenic treatment of two DDIT3 expressing cell lines induced lipid accumulation in small subpopulations only. Our results suggest a dual, promoting and limiting, role for DDIT3 in the formation of lipoblasts and liposarcoma morphology.
Sahlgrenska Cancer Center, Department of Pathology, Institute of Biomedicine, University of Gothenburg, P.O. Box 425, 40530 Gothenburg, Sweden.
Christina
0000-0003-1736-3732
C
Kåbjörn Gustafsson
Department of Oncology, Institute of Medical Sciences, University of Gothenburg, Gothenburg, Sweden.
Katarina
K
Engström
Sahlgrenska Cancer Center, Department of Pathology, Institute of Biomedicine, University of Gothenburg, P.O. Box 425, 40530 Gothenburg, Sweden.
Pierre
0000-0002-1482-8875
P
Aman