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.
Juneja
H S
HS
Department of Internal Medicine, University of Texas Health Sciences Center, Houston 77030.
Schmalsteig
F C
FC
Lee
S
S
Chen
J
J
D000911:Antibodies, Monoclonal / Q000032:analysis / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology; D001853:Bone Marrow / Q000737:chemistry / Q000473:pathology*; D002448:Cell Adhesion / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000276:immunology / Q000502:physiology*; D002460:Cell Line; D005455:Fluorescent Antibody Technique; D006412:Hematopoietic Stem Cells / Q000737:chemistry / Q000473:pathology*; D006801:Humans; D019012:Integrin beta1; D015847:Interleukin-4 / Q000494:pharmacology; D007938:Leukemia / Q000473:pathology*; D008223:Lymphoma / Q000737:chemistry / Q000473:pathology*; D016029:Receptors, Very Late Antigen / Q000032:analysis / Q000276:immunology / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D019012:Integrin beta1; D016029:Receptors, Very Late Antigen; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D015847:Interleukin-4