Many neoplasms seem to be heterogeneous in nature1,2, producing metastases by pre-existing variant cells3,4 with inherent biochemical and biological properties. The survival and proliferation of metastatic cells depend on various biological properties, such as enzymes which degrade basement membranes5, resistance to various host defence systems6,7, association with host cellular components8, adhesiveness9 and expression of certain membrane glycoproteins10,11. Recent studies have indicated that metastatic cells may differ from the local tumour cells in the expression of immune recognizable membrane-associated antigens 12,13. Such antigenic differences may result from an immunoselection of cells with distinct antigenic properties due to a specific immune response evoked against the local tumour. In view of the role of the major histocompatibility complex (MHC) system in controlling and restricting the function of immune effector cells against modified self-components 14,15, one could assume that the modulation of the expression of MHC-encoded antigens on the membrane of tumour cells influenced the interclonal relationship within a local heterogeneous tumour cell population and the subsequent generation of metastasis. The modulation of the expression of H-2 antigens on several murine tumours is well documented16,17; however, practically no attempts were made to relate H-2 modulation with invasiveness. We now describe principal differences in the expression of H-2 parental haplotypes between a local Fl methylcholanthrene-induced tumour and its descendant pulmonary metastases. These results suggest that both the expression and the immunogenicity of MHC products strongly influence the immune relationship between the tumour and the host's immune system, thus determining the generation and dissemination of metastases.
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