Transcriptomic profile induced in bone marrow mesenchymal stromal cells after interaction with multiple myeloma cells: implications in myeloma progression and myeloma bone disease

[EN]Despite evidence about the implication of the bone marrow (BM) stromal microenvironment in multiple myeloma (MM) cell growth and survival, little is known about the effects of myelomatous cells on BM stromal cells. Mesenchymal stromal cells (MSCs) from healthy donors (dMSCs) or myeloma patients...

Descripción completa

Detalles Bibliográficos
Autores: García Gómez, Antonio, Rivas Sanz, Javier de las, Ocio San Miguel, Enrique M., Díaz Rodríguez, María Elena, Montero González, Juan Carlos, Martín Alonso, María Montserrat, Blanco Blanco, Juan Francisco, Sánchez Guijo Martín, Fermín, Pandiella Alonso, Atanasio, San Miguel Izquierdo, Jesús Fernando, Garayoa Berrueta, Mercedes
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2014
País:España
Institución:Universidad de Salamanca (USAL)
Repositorio:GREDOS. Repositorio Institucional de la Universidad de Salamanca
OAI Identifier:oai:gredos.usal.es:10366/167996
Acceso en línea:http://hdl.handle.net/10366/167996
Access Level:acceso abierto
Palabra clave:Multiple myeloma
Bone marrow mesenchymal stromal cells
Tumor-stroma interactions
Gene expression profiling
Co-culture techniques
Myeloma bone disease
Bone Marrow Cells
Disease Progression
Cluster Analysis
Bone Diseases
Gene Expression Regulation
Humans
Cell Line
Cell Communication
Tumor Microenvironment
Multiple Myeloma
RNA
Gene Expression Profiling
Gene Regulatory Networks
Stem Cell Niche
Coculture Techniques
Signal Transduction
3207.08 Hematología
2302 Bioquímica
transducción de señales
humanos
comunicación celular
línea celular
ARN
mieloma múltiple
análisis por grupos
técnicas de cocultivo
perfiles de expresión génica
regulación de la expresión génica
enfermedades óseas
progresión de la enfermedad
redes génicas reguladoras
células de la médula ósea
microambiente tumoral
nicho de células madre
Descripción
Sumario:[EN]Despite evidence about the implication of the bone marrow (BM) stromal microenvironment in multiple myeloma (MM) cell growth and survival, little is known about the effects of myelomatous cells on BM stromal cells. Mesenchymal stromal cells (MSCs) from healthy donors (dMSCs) or myeloma patients (pMSCs) were co-cultured with the myeloma cell line MM.1S, and the transcriptomic profile of MSCs induced by this interaction was analyzed. Deregulated genes after co-culture common to both d/pMSCs revealed functional involvement in tumor microenvironment cross-talk, myeloma growth induction and drug resistance, angiogenesis and signals for osteoclast activation and osteoblast inhibition. Additional genes induced by co-culture were exclusively deregulated in pMSCs and predominantly associated to RNA processing, the ubiquitine-proteasome pathway, cell cycle regulation, cellular stress and non-canonical Wnt signaling. The upregulated expression of five genes after co-culture (CXCL1, CXCL5 and CXCL6 in d/pMSCs, and Neuregulin 3 and Norrie disease protein exclusively in pMSCs) was confirmed, and functional in vitro assays revealed putative roles in MM pathophysiology. The transcriptomic profile of pMSCs co-cultured with myeloma cells may better reflect that of MSCs in the BM of myeloma patients, and provides new molecular insights to the contribution of these cells to MM pathophysiology and to myeloma bone disease.

Similares en LA Referencia