Selective suppression of metastasis but not tumorigenicity of a mouse lung carcinoma by cell hybridization

Somatic cell hybrids were produced by polyethylene glycol‐induced cell fusion between metastatic CMT167 (HGPRT−/OUAR) C57BL/Icrfat mouse lung carcinoma cells and 2 non‐metastatic cell lines: C3H/He mouse L‐M(TK−) cells of mesenchymal origin and EJ (OUAS) human bladder carcinoma cells. Fusion of 2 different CMT167 (HGPRT−) clones with L‐M(TK−) cells followed by selection in HMT medium gave rise to 14 intraspecific hybrids, which were shown to express H‐2 antigens specific for both the C57 and C3H mouse strains. Three interspecific hybrids arising from fusion of EJ(OUAS) and CMT167(HGPRT−/OUAR) cells were selected in HMT/ouabain medium and characterized by human isozyme analysis. All the hybrids produced large tumours after subcutaneous inoculation of 5 × 105 cells into adult athymic nu/nu mice. The intraspecific hybrid tumours were predominantly sarcomatous (mesenchymal) in structure but a few contained epithelial acini. Metastatic ability (as assessed by production of lung metastases) was completely suppressed in 13 of the 14 mouse/mouse hybrid cell clones. These results suggest that tumorigenicity, tumour structure and the ability to metastasize are expressed independently. The interspecific hybrids, which had not retained a full human chromosome complement, produced metastatic tumours that remained epithelial in structure.