Malignant fibrous histiocytoma (MFH) is a soft tissue cancer commonly diagnosed in late adult life. New data generated by a team of researchers from Columbia University and Memorial Sloan-Kettering Cancer Center has provided insight into both the molecular mechanisms of MFH development and the cells from which the cancer originates.
In the study, a cell line derived from an individual with MFH was found to be genetically and immunohistochemically similar to undifferentiated human mesenchymal stem cells (MSCs) -- the cells that give rise to soft tissues.
Further analysis revealed that proliferating MSCs and the MFH cell line expressed high levels of a protein known as DKK1, which inhibits signaling by a group of proteins known as Wnts. Sustained inhibition of Wnt signaling in MSCs prevented them from differentiating and they became cancerous, developing tumors similar to MFH when transplanted into mice.
By contrast, restoring Wnt signaling in MFH cells caused them to differentiate and lose their cancerous characteristics. The authors therefore have suggested that MSCs are the apparent cells of origin of MFH and that reprogramming MFH cells to differentiate might provide a therapeutic strategy for treating individuals with MFH.
Article: Derivation of sarcomas from mesenchymal stem cells via inactivation of the Wnt pathway, Journal of Clinical Investigation, October 18, 2007
Materials provided by Journal of Clinical Investigation. Note: Content may be edited for style and length.
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