Phenotypic modulation in cisplatin-resistant cloned cells derived from transplantable rat malignant fibrous histiocytoma.

Abstract

The histogenesis of malignant fibrous histiocytoma (MFH) was studied using cisplatin (CDDP)-resistant MT-R8 and MT-R9 cells derived from cloned undifferentiated MT-8 and fibrohistiocytic MT-9 cells, respectively, which had been established from transplantable rat MFH. CDDP concentrations required for 50% suppression of proliferation of MT-R8 and MT-R9 cells were 5.4- and 3.3-fold greater than those of parental MT-8 and MT-9, respectively. MT-R8 and MT-R9 showed the higher positive rates to histiocytic lysosomal/ antigenic (ED1 and ED2) markers. The number of alpha-smooth muscle actin (SMA)-positive cells significantly increased in MT-R8; SMA-positive cells were also observed in MT-R9, but no difference was seen between MT-9 and MT-R9. MT-R8 and MT-R9 expressed both histiocytic and myofibroblastic phenotypes. However, the histology of subcutaneous tumors induced in syngeneic rats by MT-R8 and MR-R9 did not always reflect their in vitro nature. MT-R8 developed undifferentiated 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, osteosarcoma-like areas, collagen-rich areas containing well-developed fibroblasts and areas involving many lipoblasts. These in vivo observations suggest the multidirectional differentiation of MT-R9 cells. Phenotypic modulation of rat MFH cells seemed to be easily induced by CDDP. A possible histogenesis of MFH was discussed based on the data collected.