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 other chemotactic factors that act on receptors that signal through Gi proteins. It seems likely that the colonization of tissues during dissemination of hematopoietic tumor cells is similarly regulated. In fact, dissemination of a T-cell hybridoma, a model for T lymphoma, was blocked when Gi proteins were inactivated by the S1 catalytic subunit of pertussis toxin that had been transfected into those cells. Pertussis toxin S1 blocked dissemination of MDAY-D2 murine myeloid leukemia cells to the liver and spleen, as in T-cell hybridoma cells, but it did not prevent bone marrow colonization. In contrast, overexpression of a function-defective mutant of the Gq/11 protein blocked dissemination to the bone marrow and also prevented Gq/11 dissemination to the liver and spleen. This indicates that the influx of these myeloid cells into all tissues requires the Gq/11 protein in addition to the Gi protein in the liver and spleen. (Blood. 2000;96:691-698)
Soede
R D
RD
Divisions of Cell Biology and Molecular Genetics, The Netherlands
Wijnands
Y M
YM
Kamp
M
M
van der Valk
M A
MA
Roos
E
E
D000818:Animals; D001853:Bone Marrow / Q000473:pathology*; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000502:physiology*; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D019204:GTP-Binding Proteins / Q000502:physiology*; D015870:Gene Expression; D007951:Leukemia, Myeloid / Q000473:pathology*; D017254:Leukemic Infiltration; D008099:Liver / Q000473:pathology*; D051379:Mice; D008811:Mice, Inbred DBA; D009368:Neoplasm Transplantation; D037342:Pertussis Toxin; D013154:Spleen / Q000473:pathology*; D014162:Transfection; D014407:Tumor Cells, Cultured; D010566:Virulence Factors, Bordetella / Q000235:genetics / Q000494:pharmacology
D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D043802:GTP-Binding Protein alpha Subunits, Gq-G11