Adhesion of precursor-B acute lymphoblastic leukaemia cells to bone marrow stromal proteins.
Adhesion to bone marrow stroma is a key event in normal B lymphopoiesis, allowing exposure of B-cell progenitors to regulatory cytokines. In order to investigate whether similar processes are important in the proliferation of acute lymphoblastic leukaemia (ALL) cells of precursor-B type, the expression of various adhesion molecules was examined. By flow cytometry analysis, CD-44 and the integrins VLA-4 and VLA-5 were the most prominent. CD-44 and VLA-4 were expressed on all 18 cases of precursor-B ALL analysed, while VLA-5 was found on 15 of 18 cases. The integrin CD-11a was detected on 8 of 11 cases, while its ligand, CD-54, was present in 6/12. Other adhesion proteins such as beta 3 integrin, CD-56, CD-15, and Leu8 were not expressed to any significant extent. In view of the known binding of VLA-4 and VLA-5 to extracellular fibronectin (FN), the adhesion of leukaemic cells to FN was evaluated in a colorimetric assay. The precursor-B ALL cell lines REH and KM-3, and 7/15 cases of precursor-B ALL, showed detectable binding to FN. Binding to the other extracellular matrix proteins collagen type 1 and vitronectin was not observed, although two ALL cases showed some binding to laminin. The functional activity of the VLA-4 and VLA-5 molecules was examined using an inhibitory peptide and monoclonal antibodies. These studies indicated that ALL cells adhere to soluble fibronectin predominantly through the VLA-5 molecule (blockable with the PHM-2 antibody and a peptide containing the RGD sequence) although binding mediated by VLA-4 was also apparent in some experiments (blockable by a 40 kDa fragment containing the heparin-binding domain of FN and inhibitory antibodies). These results indicate that precursor-B ALL cells may adhere to marrow stroma through interaction of VLA-4 and VLA-5 with FN, although other mechanisms of adhesion may be important.
Makrynikola
V
V
Haematology Department, Westmead Hospital, New South Wales, Australia.
Bradstock
K F
KF
D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000378:metabolism*; D001402:B-Lymphocytes / Q000166:cytology*; D001853:Bone Marrow / Q000473:pathology*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D006410:Hematopoiesis; D006801:Humans; D016023:Integrins / Q000378:metabolism; D007797:Laminin / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000473:pathology*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000473:pathology*; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D016023:Integrins; D007797:Laminin; D010455:Peptides