Two cell lines with epithelial cell-like characteristics established from malignant fibrous histiocytomas

Abstract

Two malignant fibrous histiocytoma (MFH) cell lines were established: one from a storiform‐pleomorph subtype and the other from a myxoid one (codes, MFH‐3 and MFH‐4). Light microscopic examination revealed large rounded cells, growing mostly separately, in both cell lines. Their ultrastructure was different in various aspects. The MFH‐3 cells showed abundant lysosomal activity, a well‐developed Golgi apparatus, and a few desmosome‐like cell contacts. The MFH‐4 cells had a well‐developed rough endoplasmic reticulum, delicate bundles of tonofilaments, the formation of pseudoacini, and the presence of small completely developed desmosomes. Based on immunostaining and immunoblotting assays of cultured cells, both cell lines expressed immunoreactivity for vimentin; cytokeratins 7, 8, and 18; desmin; and laminin, but they lacked reactivity for cytokeratins 10 and 19, neurofilament, α‐smooth muscle actin, S‐100 protein, collagen type IV, carcinoembryonic antigen, and antigens specific for macrophages. Fibronectin and, to a variable extent, glial fibrillary acid protein and epithelial membrane antigen (EMA) were detectable in MFH‐3 cells only. Furthermore, a 60‐kilodalton band was present in both cell lines which was reactive for cytokeratins 8 and 18. The MFH‐3 cells had the capacity to grow as xenografts with a carcinoma‐like pattern. The cells retained their immunoreactivity for vimentin and cytokeratin 8 and showed the presence of desmosomes. Several of these immunophenotypic features also were noticed in established sarcoma cell lines and in short‐term cultures of fibroblasts, smooth muscle cells, and endothelial cells. However, experimental data on the two MFH cell lines show that the MFH cell line may express some immunophenotypic and ultrastructural features considered to be specific for epithelial cells. The MFH cells may originate from multipotential mesenchymal cells with a capacity to differentiate to fibroblast‐like cells, and less frequently, to epithelial cells, smooth muscle cells, and Schwannian cells. Such a differentiation became evident when these cells were adapted to culture conditions or grew in nude mice.

The Rise and Fall of Malignant Fibrous Histiocytoma

“…In addition to smooth muscle and histiocytic differentiation, fibroblasts also are capable of cytokeratin protein expression indicative of epithelial differentiation, notably in cases of MFH [52,[60][61][62][63][64][65][66]. In the cases of MFH expressing cytokeratin proteins, the number of immunoreactive cells varies from only 1% to a high of 32%.…”

Establishment and characterization of cell line TNMY1 derived from human malignant fibrous histiocytoma

“…Some of the confusion regarding MFH is attributable to the fact that the origin of this tumor is still unclear, due to its pleomorphic appearance. Several researchers have reported the establishment of cell lines of MFH to try to elucidate the pathogenesis of MFH 7–15 . The results have not been consistent with each other and thus the pathogenesis of MFH is still being debated.…”

Pathology of soft‐tissue tumors: Daily diagnosis, molecular cytogenetics and experimental approach

“…MFH is a typical pleomorphic sarcoma, which has been considered to be the most frequent high‐grade neoplasm among STS of adults 9,11,12,163,166–168 . The cellular origin of MFH has long been unknown, although different theories claimed that the tumor originates from histiocytes, fibroblasts, or primitive mesenchymal cells 8,9,12,114,115,163,166–180 . Fletcher postulated that pleomorphic MFH is a non‐cohesive heterogeneous group of poorly differentiated neoplasms.…”