| RRC ID |
39606
|
| Author |
Michigami T, Shimizu N, Williams PJ, Niewolna M, Dallas SL, Mundy GR, Yoneda T.
|
| Title |
Cell-cell contact between marrow stromal cells and myeloma cells via VCAM-1 and alpha(4)beta(1)-integrin enhances production of osteoclast-stimulating activity.
|
| Journal |
Blood
|
| Abstract |
Myeloma is a unique hematologic malignancy that exclusively homes in the bone marrow and induces massive osteoclastic bone destruction presumably by producing cytokines that promote the differentiation of the hematopoietic progenitors to osteoclasts (osteoclastogenesis). It is recognized that neighboring bone marrow stromal cells influence the expression of the malignant phenotype in myeloma cells. This study examined the role of the interactions between myeloma cells and neighboring stromal cells in the production of osteoclastogenic factors to elucidate the mechanism underlying extensive osteoclastic bone destruction. A murine myeloma cell line 5TGM1, which causes severe osteolysis, expresses alpha(4)beta(1)-integrin and tightly adheres to the mouse marrow stromal cell line ST2, which expresses the vascular cell adhesion molecule-1 (VCAM-1), a ligand for alpha(4)beta(1)-integrin. Co-cultures of 5TGM1 with primary bone marrow cells generated tartrate-resistant acid phosphatase-positive multinucleated bone-resorbing osteoclasts. Co-cultures of 5TGM1 with ST2 showed increased production of bone-resorbing activity and neutralizing antibodies against VCAM-1 or alpha(4)beta(1)-integrin inhibited this. The 5TGM1 cells contacting recombinant VCAM-1 produced increased osteoclastogenic and bone-resorbing activity. The activity was not blocked by the neutralizing antibody to known osteoclastogenic cytokines including interleukin (IL)-1, IL-6, tumor necrosis factor, or parathyroid hormone-related peptide. These data suggest that myeloma cells are responsible for producing osteoclastogenic activity and that establishment of direct contact with marrow stromal cells via alpha(4)beta(1)-integrin/VCAM-1 increases the production of this activity by myeloma cells. They also suggest that the presence of stromal cells may provide a microenvironment that allows exclusive colonization of myeloma cells in the bone marrow. (Blood. 2000;96:1953-1960)
|
| Volume |
96(5)
|
| Pages |
1953-60
|
| Published |
2000-9-1
|
| PII |
S0006-4971(20)54476-5
|
| PMID |
10961900
|
| MeSH |
Acid Phosphatase / metabolism
Animals
Antibodies, Monoclonal / immunology
Antibodies, Monoclonal / pharmacology
Antigens, CD / metabolism
Bone Marrow Cells / cytology
Bone Marrow Cells / metabolism*
Bone Resorption / physiopathology
CHO Cells
Cell Adhesion / drug effects
Cell Communication*
Coculture Techniques
Cricetinae
Culture Media, Conditioned / pharmacology
Female
Gene Expression
Humans
Integrin alpha4
Integrin alpha4beta1
Integrins / genetics
Integrins / immunology
Integrins / metabolism*
Isoenzymes / metabolism
Mice
Mice, Inbred C57BL
Multiple Myeloma / metabolism
Multiple Myeloma / pathology
Neutralization Tests
Osteoclasts / cytology
Osteoclasts / drug effects
Osteoclasts / physiology*
Protein Binding
RNA, Messenger / genetics
RNA, Messenger / metabolism
Rats
Receptors, Lymphocyte Homing / genetics
Receptors, Lymphocyte Homing / immunology
Receptors, Lymphocyte Homing / metabolism*
Recombinant Proteins / metabolism
Solubility
Stromal Cells / cytology
Stromal Cells / metabolism*
Tartrate-Resistant Acid Phosphatase
Tumor Cells, Cultured
Vascular Cell Adhesion Molecule-1 / genetics
Vascular Cell Adhesion Molecule-1 / immunology
Vascular Cell Adhesion Molecule-1 / metabolism*
|
| IF |
17.794
|
| Times Cited |
174
|
|
WOS Category
|
HEMATOLOGY
|
| Resource |
| Human and Animal Cells |
ST2(RCB0224) |
