EXPRESSION OF PERTUSSIS TOXIN ADENOSINE-DIPHOSPHATE RIBOSYLTRANSFERASE IN A T-CELL HYBRIDOMA REDUCES METASTATIC CAPACITY

T-cell hybridomas are highly metastatic, and their in vitro invasivene ss correlates with metastatic capacity. Invasion is blocked by pertuss is toxin (PT), which adenosine diphosphate (ADP)-ribosylates G(i)-prot eins, and we have provided evidence that the PT-sensitive signal stimu lates leukocyte function-associated antigen-1 (LFA-1)-mediated adhesio n required for invasion. PT pretreatment of TAM2D2 T-cell hybridoma ce lls reduced metastasis, but only to a limited extent. In the present s tudy, we have transfected the cDNA of the PT ADP-ribosyltransferase S1 subunit into TAM2D2 cells to abrogate G(i)-protein function permanent ly. We report here a substantial reduction in the metastatic capacity of two transfectants, S05 and S09, in which 88% and 95% of the G(i)-pr oteins was ADP-ribosylated. Two-thirds of the mice injected with S09 c ells were tumor-free. Metastasis to the liver was almost completely pr evented and less metastases were formed in the spleen and kidneys. Met astasis formation by S05 cells in liver and spleen was much reduced, b ut in lymph nodes and peritoneal tissues, metastases occurred with a f requency similar to that of controls. We conclude that G(i)-proteins p lay an important role in T-cell hybridoma metastasis. We propose that the reduction in metastasis is due to diminished entry of tumor cells from the blood into tissues. (C) 1996 by The American Society of Hemat ology.