Adhesive interactions of human multiple myeloma cell lines with different extracellular matrix molecules.
Multiple myeloma represents a human B cell malignancy which is characterized by a predominant localization of the malignant cell clone within the bone marrow. With the exception of the terminal stage of the disease the myeloma tumor cells do not circulate in the peripheral blood. The bone marrow microenvironment is believed to play an important role in homing, proliferation and terminal differentiation of myeloma cells. Here we have studied the expression of several extracellular matrix (ECM) molecules in the bone marrow of multiple myeloma patients and analyzed their adhesive capacities with four different human myeloma-derived cell lines. All ECM molecules analyzed (tenascin, laminin, fibronectin, collagen types I, III, V and VI) could be detected in bone marrow cryostat sections of multiple myeloma patients. Adhesion assays showed that only laminin, the microfibrillar collagen type VI and fibronectin were strong adhesive components for the myeloma cell lines U266, IM-9, OPM-2 and NCI-H929. Tenascin and collagen type I were only weak adhesive substrates for these myeloma cells. Adhesion to laminin and fibronectin was beta 1-integrin-mediated since addition of anti-beta 1-integrin antibodies could inhibit the binding of the four different cell types to both matrix molecules. In contrast, integrins do not seem to be involved in binding of the myeloma cells to collagen type VI. Instead, inhibition of binding by heparin suggested that membrane-bound heparan sulfate proteoglycans are responsible ligands for binding to collagen type VI. Adhesion assays with several B-cell lines resembling earlier differentiation stages revealed only weak interactions with tenascin and no interactions with collagen type VI, laminin or fibronectin. In summary, the interactions of human myeloma cells with the extracellular matrix may explain the specific retention of the plasma cells within the bone marrow.
Kibler
C
C
University Medical Clinic, Dept. II, Tübingen, FRG.
Schermutzki
F
F
Waller
H D
HD
Timpl
R
R
Müller
C A
CA
Klein
G
G
D000818:Animals; D000906:Antibodies; D002448:Cell Adhesion / Q000502:physiology; D003094:Collagen / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005434:Flow Cytometry; D015870:Gene Expression / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D006801:Humans; D019012:Integrin beta1 / Q000032:analysis / Q000235:genetics; D007797:Laminin / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics; D009101:Multiple Myeloma; D011485:Protein Binding / Q000502:physiology; D011509:Proteoglycans / Q000235:genetics; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053667:Syndecans; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000166:cytology / Q000378:metabolism
D000906:Antibodies; D016326:Extracellular Matrix Proteins; D019012:Integrin beta1; D007797:Laminin; D008562:Membrane Glycoproteins; D011509:Proteoglycans; D053667:Syndecans; D003094:Collagen