Adipogenic, osteogenic and myofibrogenic differentiations of a rat malignant fibrous histiocytoma (MFH)-derived cell line, and a relationship of MFH cells with embryonal mesenchymal, perivascular and bone marrow stem cells

Abstract

Malignant fibrous histiocytoma (MFH) is regarded as an undifferentiated pleomorphic sarcoma with unproven histogenesis. We investigated pathobiological characteristics of a rat MFH cell line (MT-9). Immunocytochemically, MT-9 cells and MT-9-induced tumours reacted to vimentin, A3 (rat MFH cell-specific antibody), macrophage markers and α-SMA (myofibroblastic marker), indicating that MT-9 showed both histiocytic and (myo)fibroblastic features. Adipogenic supplement-added MT-9 showed increased accumulation of lipid droplets. Addition of BMP-2 or osteogenic supplement to MT-9 enhanced osteoblastic markers (ALP activity, osteocalcin mRNA expression and calcification). TGF-β1-treated MT-9 revealed increased numbers of α-SMA-immunopositive cells, and enhanced protein levels of α-SMA and fibronectin, indicating myofibrogenesis. In rat tissues, A3 labelled with immature mesenchymal and perivascular cells in foetuses and neonates, and with marrow stem cells in adults. c-kit mRNA expression was seen in bone marrows and MT-9. Collectively, progenitors of MFH should be sought in lineage of marrow stem cells capable of differentiating into mesenchymal cells.