Vascular cell adhesion molecule-1 and VLA-4 are obligatory adhesion proteins in the heterotypic adherence between human leukemia/lymphoma cells and marrow stromal cells.

We have utilized two well-characterized human leukemia/lymphoma (LL) cell lines, UTMB-460 and CEM, to determine the role of integrin very late antigen-alpha 4 beta 1 (VLA-4) and its ligand vascular cell adhesion molecule-1 (VCAM-1) in the adherence of the LL cells to marrow stromal cells (MSC). Both these LL cell lines express alpha and beta subunits of VLA-4. VCAM-1 is constitutively expressed by human MSC and its expression can be upregulated by interleukin-4 (IL-4) and recombinant human tissue necrosis factor-alpha (rTNF-alpha). IL-4 and rTNF-alpha stimulation of MSC is associated with a significant increase in the adherence of both UTMB-460 and CEM LL cells to the cytokine-stimulated MSC. Monoclonal antibodies directed against the alpha and beta subunits of VLA-4 and VCAM-1 significantly inhibit adherence of the LL cells to unstimulated and cytokine-treated MSC. The data reported indicate that VCAM-1 and integrin VLA-4 are obligatory adhesion proteins in the heterotypic adherence between human LL cells and MSC. The constitutive expression of VCAM-1 by MSC may be partially responsible for retention of leukemia cells in th bone marrow and metastasis of lymphomas to the bone marrow.