CELLS SECRETING TUMOR-NECROSIS-FACTOR SHOW ENHANCED METASTASIS IN NUDE-MICE

A tumour cell may acquire the ability to invade and metastasie via heritable changes in its genome and/or changes in the local environment. Chinese hamster ovary (CHO) cells transfected with the gene for human TNF (CHO/TNF cells) showed a greatly enhanced ability to invade peritoneal surfaces and metastasise in nude mice compared with cells transfected by the vector alone. In situ hybridisation with a riboprobe for human TNF showed that the CHO/TNF cells were actively transcribing this cytokine after in vivo injection. Neutralising antibodies to human TNF, both whole IgG and F(ab)2 fragments, abrogated the enhanced metastatic activity of the TNF-secreting cells. Thus transfection of a cytokine/growth-factor gene can confer a metastatic phenotype on the recipient cell.