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N-cadherin-mediated interaction with multiple myeloma cells inhibits osteoblast differentiation.
- Source :
-
Haematologica [Haematologica] 2011 Nov; Vol. 96 (11), pp. 1653-61. Date of Electronic Publication: 2011 Aug 09. - Publication Year :
- 2011
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Abstract
- Background: Multiple myeloma is a hematologic malignancy characterized by a clonal expansion of malignant plasma cells in the bone marrow, which is accompanied by the development of osteolytic lesions and/or diffuse osteopenia. The intricate bi-directional interaction with the bone marrow microenvironment plays a critical role in sustaining the growth and survival of myeloma cells during tumor progression. Identification and functional analysis of the (adhesion) molecules involved in this interaction will provide important insights into the pathogenesis of multiple myeloma.<br />Design and Methods: Multiple myeloma cell lines and patients' samples were analyzed for expression of the adhesion molecule N-cadherin by immunoblotting, flow cytometry, immunofluorescence microscopy, immunohistochemistry and expression microarray. In addition, by means of blocking antibodies and inducible RNA interference we studied the functional consequence of N-cadherin expression for the myeloma cells, by analysis of adhesion, migration and growth, and for the bone marrow microenvironment, by analysis of osteogenic differentiation.<br />Results: The malignant plasma cells in approximately half of the multiple myeloma patients, belonging to specific genetic subgroups, aberrantly expressed the homophilic adhesion molecule N-cad-herin. N-cadherin-mediated cell-substrate or homotypic cell-cell adhesion did not contribute to myeloma cell growth in vitro. However, N-cadherin directly mediated the bone marrow localization/retention of myeloma cells in vivo, and facilitated a close interaction between myeloma cells and N-cadherin-positive osteoblasts. Furthermore, this N-cadherin-mediated interaction contributed to the ability of myeloma cells to inhibit osteoblastogenesis.<br />Conclusions: Taken together, our data show that myeloma cells frequently display aberrant expression of N-cadherin and that N-cadherin mediates the interaction of myeloma cells with the bone marrow microenvironment, in particular the osteoblasts. This N-cadherin-mediated interaction inhibits osteoblast differentiation and may play an important role in the pathogenesis of myeloma bone disease.
- Subjects :
- Bone Marrow metabolism
Bone Marrow pathology
Bone Marrow Cells metabolism
Bone Marrow Cells pathology
Cadherins genetics
Cell Adhesion genetics
Cell Line, Tumor
Humans
Multiple Myeloma genetics
Multiple Myeloma pathology
Neoplasm Proteins genetics
Osteoblasts pathology
Cadherins metabolism
Cell Communication
Cell Differentiation
Multiple Myeloma metabolism
Neoplasm Proteins metabolism
Osteoblasts metabolism
Tumor Microenvironment
Subjects
Details
- Language :
- English
- ISSN :
- 1592-8721
- Volume :
- 96
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Haematologica
- Publication Type :
- Academic Journal
- Accession number :
- 21828122
- Full Text :
- https://doi.org/10.3324/haematol.2010.038133