Sphingosine-1-phosphate and lysophosphatidic acid trigger invasion of primitive hematopoietic cells into stromal cell layers

A new primitive hematopoietic cell line (THS119), exhibiting Lin(-)/Sca-1()/c-Kit(+) a surface phenotype, grew and survived underneath stromal cells (TBR59). The ability of the THS119 cells to invade these stromal cell layer s was dependent on the inclusion of serum in the culture medium, This was a pparently due to a requirement for lipids contained in serum. Their invasio n of the stromal cell layers in serum-free cultures could be triggered by a ddition of sphingosine-1-phosphate (S1P) or lysophosphatidic acid (LPA) and was dependent on both Rho- and Ras-signaling pathways. Between the 2 possi ble receptors of S1P and LPA, edg-1 and edg-2, expression of edg-2 only was found to be correlated with immaturity and/or invasive activity of the pri mitive hematopoietic cells. These results suggest the importance of specifi c lipids and their specific receptors on the invasive activity of primitive hematopoietic cells in the hematopoietic microenvironment. (Blood. 2000;96 :139-144) (C) 2000 by The American Society of Hematology.