Clemens Sorg

Cell-Surface Structure and State of Malignancy in Human Malignant Melanoma

Human malignant melanoma is a spontaneous tumor that progresses from the initial premalignant lesions to highly metastatic forms. Clinical and histological observations of this process and some recent knowledge gained on experimental tumor models suggest that tumor progression is a complex multistage process. In the course of this process, several distinct properties have to be aquired by the tumor cells either sequentially or in parallel (Poste and Fidler, 1980; Nicolson et al., 1977). Properties of prime importance are believed to be invasiveness, neovascularization, resistance to rejection mechanisms, and adaptation to and growth in a different organ or tissue. It has been shown in animal tumor models that the capacity to metastasize is a phenotypically expressed property of a tumor cell; moreover, even the target organ seems to be predetermined by the phenotype (Dexter et al., 1978; Hart and Fidler, 1980; Nicolson and Winkelhake, 1975; Nicolson et al.,1978; Nowell, 1976; Schirrmacher et al., 1979a; Susuki et al., 1978). The mechanisms by which primary tumors develop highly malignant variants have been circumscribed by the term retrodifferentiation and are unknown (Coggin and Anderson, 1974; Renselaer Potter, 1978; Uriel, 1979). That the process of retrodifferentiation might also be reversed is indicated in experiments wherein nonmetastasizing variants were isolated from metastases (Tao and Burger, 1977). It is logical to assume that phenotypic changes that are associated with the expression of different biochemical and biological properties are also associated with changes in the cell surface, which in fact has been demonstrated in several instances (Fogel et al., 1979; Killion and Kollmorgen, 1976; Nicolson and Winkelhake, 1975; Poste, 1977; Schirrmacher et al., 1979b; Sorg et al., 1978; Yogeeswaran et al., 1978, 1979).

The Molecular Complex of Macrophage Migration Inhibitory Activity (MIF) and its Role in Inflammatory Reactions

The macrophage migration inhibitory factor (MIF), the first lymphokine ever to be described (1, 2) is released by cultivated lymph node, spleen or peripheral blood mononuclear cells upon antigen or mitogen stimulation. As its production is related to the state of immunity, MIF was considered to be a molecular equivalent of the delayed type hypersensitive (DTH) state. By chemical characterization it became clear that MIF activity was associated with a group of molecules, whose molecular weight ranged from below 10,000 to greater than 60,000 D. Biological activity was found after isoelectric focussing at a pH of 5 and 3. The data obtained were similar with MIF from mitogen-stimulated mouse, guinea pig and human peripheral blood mononuclear cells (3).