Gi and Gq/11 proteins are involved in dissemination of myeloid leukemia cells to the liver and spleen, whereas bone marrow colonization involves Gq/11 but not Gi

The migration of leukocytes into tissues is regulated by chemokines and oth er chemotactic factors that act on receptors that signal through Gi protein s. It seems likely that the colonization of tissues during dissemination of hematopoietic tumor cells is similarly regulated. In fact, dissemination o f a T-cell hybridoma, a model for T lymphoma, was blocked when Gi proteins were inactivated by the S1 catalytic sub-unit of pertussis toxin that had b een transfected into those cells. Pertussis toxin S1 blocked dissemination of MDAY-D2 murine myeloid leukemia cells to the liver and spleen, as in T-c ell hybridoma cells, but it did not prevent bone marrow colonization. In co ntrast, overexpression of a function-defective mutant of the Gq/11 protein blocked dissemination to the bone marrow and also prevented Gq/11 dissemina tion to the liver and spleen. This indicates that the influx of these myelo id cells into all tissues requires the Gq/11 protein in addition to the Gi protein in the liver and spleen. (C) 2000 by The American Society of Hemato logy.