title: Transcriptomic profile induced in bone marrow mesenchymal stromal cells after interaction with multiple myeloma cells: implications in myeloma progression and myeloma bone disease.
abstract: 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.
authors.affiliation: Centro de Investigación del Cáncer, IBMCC (Universidad de Salamanca-CSIC), Salamanca, Spain. Hospital Universitario de Salamanca-IBSAL, Salamanca, Spain. Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León, Salamanca, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Garcia-Gomez
authors.affiliation: Centro de Investigación del Cáncer, IBMCC (Universidad de Salamanca-CSIC), Salamanca, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: De Las Rivas
authors.affiliation: Centro de Investigación del Cáncer, IBMCC (Universidad de Salamanca-CSIC), Salamanca, Spain. Hospital Universitario de Salamanca-IBSAL, Salamanca, Spain.
authors.forename: Enrique M
authors.initials: EM
authors.lastname: Ocio
authors.affiliation: Centro de Investigación del Cáncer, IBMCC (Universidad de Salamanca-CSIC), Salamanca, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Díaz-Rodríguez
authors.affiliation: Centro de Investigación del Cáncer, IBMCC (Universidad de Salamanca-CSIC), Salamanca, Spain.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Montero
authors.affiliation: Centro de Investigación del Cáncer, IBMCC (Universidad de Salamanca-CSIC), Salamanca, Spain. Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León, Salamanca, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Martín
authors.affiliation: Hospital Universitario de Salamanca-IBSAL, Salamanca, Spain.
authors.forename: Juan F
authors.initials: JF
authors.lastname: Blanco
authors.affiliation: Hospital Universitario de Salamanca-IBSAL, Salamanca, Spain. Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León, Salamanca, Spain.
authors.forename: Fermín M
authors.initials: FM
authors.lastname: Sanchez-Guijo
authors.affiliation: Centro de Investigación del Cáncer, IBMCC (Universidad de Salamanca-CSIC), Salamanca, Spain. Hospital Universitario de Salamanca-IBSAL, Salamanca, Spain.
authors.forename: Atanasio
authors.initials: A
authors.lastname: Pandiella
authors.affiliation: Centro de Investigación del Cáncer, IBMCC (Universidad de Salamanca-CSIC), Salamanca, Spain. Hospital Universitario de Salamanca-IBSAL, Salamanca, Spain. Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León, Salamanca, Spain.
authors.forename: Jesús F
authors.initials: JF
authors.lastname: San Miguel
authors.affiliation: Centro de Investigación del Cáncer, IBMCC (Universidad de Salamanca-CSIC), Salamanca, Spain. Hospital Universitario de Salamanca-IBSAL, Salamanca, Spain. Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León, Salamanca, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Garayoa
mesh_terms: D001847:Bone Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D001854:Bone Marrow Cells / Q000378:metabolism* / Q000473:pathology; D002450:Cell Communication; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D018920:Coculture Techniques; D018450:Disease Progression; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000473:pathology; D009101:Multiple Myeloma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D055153:Stem Cell Niche; D059016:Tumor Microenvironment
chemical_list: D012333:RNA, Messenger