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Yamate J, Ogata K, Yuasa T, Kuwamura M, Takenaka S, Kumagai D, Itoh K, LaMarre J: 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. Eur J Cancer. 2007 Dec;43(18):2747-56. 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 alpha-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-beta1-treated MT-9 revealed increased numbers of alpha-SMA-immunopositive cells, and enhanced protein levels of alpha-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. |
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