Rac-1 GTPase controls the capacity of human leukaemic lymphoblasts to migrate on fibronectin in response to SDF-1α (CXCL12)

Manuel Freret; Flore Gouel; Catherine Buquet; Elisabeth Legrand; Jean-Pierre Vannier; Marc Vasse; Isabelle Dubus

doi:10.1016/j.leukres.2011.03.011

Rac-1 GTPase controls the capacity of human leukaemic lymphoblasts to migrate on fibronectin in response to SDF-1α (CXCL12)

Leuk Res. 2011 Jul;35(7):971-3. doi: 10.1016/j.leukres.2011.03.011. Epub 2011 Apr 1.

Authors

Manuel Freret¹, Flore Gouel, Catherine Buquet, Elisabeth Legrand, Jean-Pierre Vannier, Marc Vasse, Isabelle Dubus

Affiliation

¹ Laboratoire MERCI (EA3829), Rouen University, and Department of Haematology, Rouen University Hospital, Rouen, France.

PMID: 21458858
DOI: 10.1016/j.leukres.2011.03.011

Abstract

Acute lymphoblastic leukaemia (ALL) is characterized by malignant cell infiltration of bone marrow, requiring chemotactic response to SDF-1α. Using time-lapse video, we measured the velocity of ALL cells on fibronectin, and found that SDF-1α increased their migration activity for 2 h, but had no effect after 4h, following internalization of its receptor CXCR4. Transfection of ALL cells with dominant-negative Rac1 mutant significantly prolonged their chemotactic response to SDF-1α, and this effect was associated with an alteration of CXCR4 internalization. These data suggest a regulatory role for Rac1 in the chemotactic response of ALL cells to SDF-1α via receptor processing.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Movement*
Chemokine CXCL12 / metabolism*
Fibronectins / metabolism*
Flow Cytometry
Humans
Precursor Cell Lymphoblastic Leukemia-Lymphoma / metabolism*
Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology*
Tumor Cells, Cultured
rac1 GTP-Binding Protein / metabolism*

Substances

CXCL12 protein, human
Chemokine CXCL12
Fibronectins
RAC1 protein, human
rac1 GTP-Binding Protein