Endoglin is a component of the transforming growth factor (TGF)-beta receptor complex of human pre-B leukemic cells.

Endoglin was first identified on a cell line derived from pre-B acute lymphoblastic leukemia. This 180-kDa homodimeric glycoprotein was then shown to be primarily expressed on endothelial cells and to bind the beta 1 and beta 3 isoforms of TGF-beta with high affinity. We now demonstrate that pre-B leukemic cells express a functional TGF-beta 1 receptor complex. The levels of mRNA for these receptors and for TGF-beta 1 were quantitated by PCR. HOON, G2, and NALM-6 cell lines express similar levels of mRNA for TGF-beta 1 and for TGF-beta receptor I (R-I) and receptor II (R-II). HOON cells express ten times more endoglin than G2 and NALM-6 cells, whereas all three cell lines have low levels of betaglycan relative to other cell types. The receptors were identified by affinity labeling with 125I-labeled TGF-beta 1, chemical cross-linking, and specific immunoprecipitation. Endoglin, R-II, and R-I were co-precipitated by Abs to either endoglin or R-II, indicating that these proteins are forming a receptor complex on leukemic cells; no betaglycan could be immunoprecipitated. The receptor complex is functional, as demonstrated by inhibition of proliferation of HOON cells (80%) and NALM-6 cells (60%) with 25 pM TGF-beta 1. Furthermore, the motility of HOON and NALM-6 cells on immobilized fibronectin, which appears to be alpha 4 beta 1-integrin mediated, was stimulated two- to threefold by TGF-beta 1. These results suggest that active TGF-beta 1 produced in the bone marrow microenvironment might stimulate the motility of normal pre-B cells and the peripheral dissemination of leukemic pre-B cells.