Suppression of malignancy in hybrid cells: the mechanism

When malignant cells, defined by their ability to grow progressively in genetically compatible hosts, are fused with diploid fibroblasts of the same species, the resulting hybrid cells, so long as they retain certain specific chromosomes donated by the diploid parent cell, are non-malignant. When these particular chromosomes are eliminated from the hybrid, the malignant phenotype reappears, and the segregant cell is again able to grow progressively in vivo. In the present experiments the histological character of the lesions produced by the inoculation of crosses between malignant and non-malignant cells was examined. It was found, in a wide range of material, and without exception, that where one or other of the parent cells in the cross was of fibroblastic lineage, malignancy was suppressed when the hybrid cells produced a collagenous extracellular matrix in vivo; and it reappeared when genetic segregants were produced that had lost the ability to produce this matrix. These results are interpreted in terms of a general model in which it is proposed that the progressive multiplication of malignant cells in vivo is a secondary consequence of a genetically stable impairment of terminal differentiation.