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 layers was dependent on the inclusion of serum in the culture medium. This was apparently due to a requirement for lipids contained in serum. Their invasion of the stromal cell layers in serum-free cultures could be triggered by addition of sphingosine-1-phosphate (S1P) or lysophosphatidic acid (LPA) and was dependent on both Rho- and Ras-signaling pathways. Between the 2 possible 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 primitive hematopoietic cells. These results suggest the importance of specific lipids and their specific receptors on the invasive activity of primitive hematopoietic cells in the hematopoietic microenvironment.