Contact of myeloma cells induces a characteristic transcriptome signature in skeletal precursor cells -Implications for myeloma bone disease

Autor: Regina Ebert, Alexander Keller, Franz Jakob, Robert J. Tower, Doris Schneider, Katrin Schlegelmilch, S. Zeck, Norbert Schütze, Julia Dotterweich, Beate Geyer
Rok vydání: 2015
Předmět:
0301 basic medicine
Male
Stromal cell
Histology
Physiology
Cellular differentiation
Endocrinology
Diabetes and Metabolism
Antigens
CD19
Osteogenic precursor cells
Cell Communication
Biology
Plasma cell
Bone and Bones
Transcriptome
03 medical and health sciences
Osteogenesis
Precursor cell
Bone disease
ddc:570
Cell Line
Tumor
medicine
Cell Adhesion
Angiopoietin-Like Protein 4
Humans
Angiopoietin-like 4
ddc:610
Multiple myeloma
Aged
B-Lymphocytes
Gene Expression Profiling
Mesenchymal stem cell
Reproducibility of Results
Cell Differentiation
Mesenchymal Stem Cells
Middle Aged
medicine.disease
Molecular biology
Coculture Techniques
Cell biology
Up-Regulation
Gene Expression Regulation
Neoplastic
030104 developmental biology
medicine.anatomical_structure
Phenotype
Female
Bone Diseases
Multiple Myeloma
Monoclonal gammopathy of undetermined significance
Zdroj: Bone. 93
ISSN: 1873-2763
Popis: Physical interaction of skeletal precursors with multiple myeloma cells has been shown to suppress their osteogenic potential while favoring their tumor-promoting features. Although several transcriptome analyses of myeloma patient-derived mesenchymal stem cells have displayed differences compared to their healthy counterparts, these analyses insufficiently reflect the signatures mediated by tumor cell contact, vary due to different methodologies, and lack results in lineage-committed precursors.To determine tumor cell contact-mediated changes on skeletal precursors, we performed transcriptome analyses of mesenchymal stem cells and osteogenic precursor cells cultured in contact with the myeloma cell line INA-6. Comparative analyses confirmed dysregulation of genes which code for known disease-relevant factors and additionally revealed upregulation of genes that are associated with plasma cell homing, adhesion, osteoclastogenesis, and angiogenesis. Osteoclast-derived coupling factors, a dysregulated adipogenic potential, and an imbalance in favor of anti-anabolic factors may play a role in the hampered osteoblast differentiation potential of mesenchymal stem cells. Angiopoietin-Like 4 (ANGPTL4) was selected from a list of differentially expressed genes as a myeloma cell contact-dependent target in skeletal precursor cells which warranted further functional analyses. Adhesion assays with full-length ANGPTL4-coated plates revealed a potential role of this protein in INA-6 cell attachment.This study expands knowledge of the myeloma cell contact-induced signature in the stromal compartment of myelomatous bones and thus offers potential targets that may allow detection and treatment of myeloma bone disease at an early stage.
Databáze: OpenAIRE
Externí odkaz: