PHENOTYPIC MODULATION IN CISPLATIN-RESISTANT CLONED CELLS DERIVED FROM TRANSPLANTABLE RAT MALIGNANT FIBROUS HISTIOCYTOMA

The histogenesis of malignant fibrous histiocytoma (MFH) was studied u sing cisplatin (CDDP)-resistant MT-R8 and MT-R9 cells derived from clo ned undifferentiated MT-8 and fibrohistiocytic MT-9 cells, respectivel y, which had been established from transplantable rat MFH. CDDP concen trations required for 50% suppression of proliferation of MT-R8 and MT -RS cells were 5.4- and 3.3-fold greater than those of parental MT-8 a nd MT-9, respectively. MT-R8 and MT-RS showed the higher positive rate s to histiocytic lysosomal/antigenic (ED1 and ED2) markers. The number of alpha-smooth muscle actin (SMA)-positive cells significantly incre ased in MT-R8; SMA-positive cells were also observed in MT-RS, but no difference was seen between MT-9 and MT-RS. MT-R8 and MT-RS expressed both histiocytic and myofibroblastic phenotypes. However, the histolog y of subcutaneous tumors induced in syngeneic rats by MT-R8 and MR-RS did not always reflect their in vitro nature, MT-R8 developed undiffer entiated sarcomas similar to parental MT-8 tumors. In contrast, MT-R9 induced tumors with polytypic histologies such as the storiform growth pattern, neoplastic growth of granular cells and myofibroblasts, oste osarcoma-like areas, collagen-rich areas containing well-developed fib roblasts and areas involving many lipoblasts. These in vivo observatio ns suggest the multidirectional differentiation of MI-RS cells. Phenot ypic modulation of rat MFH cells seemed to be easily induced by CDDP, A possible histogenesis of MFH was discussed based on the data collect ed.