Four cloned cell lines, MT‐7, MT‐8, MT‐9 and MX‐10, were established from a transplantable malignant fibrous histiocytoma (MFH) of F344 rats to investigate the histogenesis of the tumor. Cells of MT‐7, MT‐9 and MT‐10 had fine structures characteristic of histiocytes, such as numerous cell processes, many lysosomes and well‐developed cytoplasmic organelles. They stained positively for histiocytic lysosomal and antigenic markers. In addition, MT‐9 cells contained microfllaments and well‐developed RER in their cytoplasm, suggesting that they may be facultative fibroblasts. MT‐8 cells stained weakly for histiocytic markers and had scant cytoplasmic organelles. They were identified as undifferentiated mesenchymal cells. The tumors induced in syngeneic rats by inoculating MT‐7 or MT‐10 consisted of a mixture of the pleomorphic, myxoid and storiform types of MFH, and those by MT‐9 were of the storiform type. Cells forming these tumors stained positively for histiocytic markers. Tumors induced by MT‐8 consisted of undifferentiated cells negative to these stainings. The histogenesis of MFH is surmised to be related to various differentiation stages shifting from undifferentiated cells to histiocytic cells capable of acting as facultative fibroblasts.
Morphologic and functional characteristics were investigated on in vitro passaged cells (MT-P) derived from a rat transplantable malignant fibrous histiocytoma (MFH-MT). There were spindle, polygonal, and giant cell types in MT-P. Ultrastructurally, the polygonal and giant cells had the abundant cytoplasm with many lysosomes and processes, whereas the spindle cells possessed smooth cell surface and a small number of lysosomes in their cytoplasm. Immunorosette formation for Fc- and C3-surface receptors and phagocytic activity were demonstrated in 10-20% of MT-P. MT-P were positive for acid phosphatase, nonspecific esterase and alkaline phosphatase. Chromosomes counted in 100 MT-P ranged from 32 to 100 with two peaks of 64 and 76. Tumors induced in syngeneic rats by inoculating MT-P showed variable histologic patterns. They were composed partly of histiocytic cells arranged in a compact sheet. Fibroblastic cells often arranged in a storiform pattern or were supported by myxoid matrix. Osteosarcoma-like structures were occasionally found in the tumors. These results suggest that MFH-MT is heterogeneous, although some cells constituting the tumors have histiocytic markers.
A cis‐iamminedichloroplatinum (CDDP)‐selected cell line (MT‐R10) was induced by continuous exposure of an in vitro passaged cell line (MT‐P) established from a transplantable rat malignant fibrous histiocytoma (MFH‐MT) to CDDP. MT‐R10, capable of proliferating in the presence of l.0 μg CDDP/ml, was passaged in CDDP free medium. The doubling time of MT‐R10 at passage 10 (MT ‐R10/10) was almost the same as that of MT ‐P, being 22.3 and 25.5 h, respectively. The concentration of CDDP required for 50% inhibition of MT‐R10/10 proliferation was two‐fold higher than that of MT‐P. MT‐R10 consisted of round, epithelial‐type cells arranged in compact sheets. Ultrastructurally, MT‐R10 had numerous free ribosomes, some mitochondria, and other poorly developed cytoplasmic or‐ganelles suggesting its undifferentiated nature. MT ‐R10 showed no reaction for acid phosphatase or non‐specific esterase. Tumors induced in syngeneic rats by inoculation with MT‐R10 consisted of small, round, undifferentiated cells with scanty cytoplasm. They showed organoid and trabecular patterns, and were often arranged in compact sheets. The neoplastic cells showed no reaction for any of the histiocytic lysosomal and antigenic markers tested, but exhibited a strong reaction for alkaline phosphatase. Bone formation was often observed in the tumors. These observations suggest that CDDP selected, undifferentiated cells may have osteogenic potential and may be one of the progenitor cells of MFH‐MT.
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