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.
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.
Laboratory of Veterinary Pathology, Life and Environmental Sciences, Osaka Prefecture University, Gakuencho 1-1, Sakai, Osaka 599-8531, Japan. yamate@vet.osakafu-u.ac.jp
Jyoji
J
Yamate
Keiko
K
Ogata
Takahiro
T
Yuasa
Mitsuru
M
Kuwamura
Shigeo
S
Takenaka
Daijirou
D
Kumagai
Kazuyuki
K
Itoh
Jonathan
J
LaMarre
D017667:Adipocytes / Q000473:pathology*; D000818:Animals; D001854:Bone Marrow Cells / Q000473:pathology*; D002114:Calcinosis / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000502:physiology; D045744:Cell Line, Tumor; D005260:Female; D053686:Fetal Stem Cells / Q000473:pathology*; D051677:Histiocytoma, Malignant Fibrous / Q000378:metabolism / Q000473:pathology*; D007150:Immunohistochemistry; D008297:Male; D059630:Mesenchymal Stem Cells / Q000473:pathology*; D009368:Neoplasm Transplantation; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344
D012333:RNA, Messenger; D019009:Proto-Oncogene Proteins c-kit