Cellular heterogeneity. Explanation for changing of tumor phenotype and biologic behavior in soft tissue sarcomas

Many human soft tissue sarcomas are known to show variable structures in a given tumor and to be able of changing the histological feature during the course of the disease. These facts prompted an experimental study in order to ascertain if by use of long-term cultures of an established rat fibrosarcoma cell line (RFS) in respective inoculation tumors a histological picture different from the original fibrosarcoma could be produced. It was found that inoculation tumors generated by later subcultures partly corresponded to tumors with features of malignant histiocytomas and malignant fibrous histiocytomas. In a further experiment we attempted to initiate metastatic dissemination of a primarily non-metastasizing xenotransplanted RFS sarcoma in nude mice. By repeated diminution operations comparable to inadequate tumor surgery in human metastasis formation in lung parenchyme was attained. Taking into account cellular heterogeneity as basically responsible for the phenomena observed, different causal aspects concerning the experimental results are discussed. We deduce from our findings that the concept of histogenetic classification of soft tissue sarcomas should be replaced by an interpretation according to the actual differentiation. This also applies to malignant fibrous histiocytomas which are at least in part mesenchymal tumors and not descendants of mononuclear phagocytic cells and may originate by a dedifferentiation process of otherwise defined sarcoma types.