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Bone osteoblastic and mesenchymal stromal cells lack primarily tumoral features in multiple myeloma patients

Leukemia volume 24, pages 1368–1370 (2010)Cite this article

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Multiple myeloma (MM) is characterized by a close relationship between tumor and bone microenvironment cells, which supports the survival of MM cells and determines a severe impairment of bone homeostasis.1 Mesenchymal stromal cells (MSCs) and osteoblasts (OBs) assume a critical role in this process either through the overproduction of growth factors and osteoclastogenic molecules or by undergoing alterations responsible for the suppression of bone formation that rarely repairs even after disease remission.2 This suggests that both types of cells could be primarily involved in the tumoral process. Alterations of gene expression and genomic profiles have been reported in MSCs of MM patients in comparison with healthy donors as published in Leukemia.3, 4 Moreover, we have recently shown the occurrence of different patterns of gene expression profile, not only in MSCs but also in OBs of MM patients compared with healthy individuals and in relationship to MM bone disease.5 Nevertheless, it is still unclear whether these bone microenvironment cells in MM patients are primarily tumoral. To clarify this issue, we analyzed the genomic profiles and the presence of telomere maintenance mechanisms of bone-derived MSCs and OBs obtained from a cohort of 26 MM patients at diagnosis, 7 monoclonal gammopathy of undetermined significance (MGUS) patients and 8 healthy donors (N) who underwent orthopedic surgery. Samples were checked for gene expression profiling by microarray as published earlier.5 Baseline characteristics of the MM patients together with genetic alterations of purified CD138+ MM cells are reported in Table 1.

Table 1 Characteristics of MM patients
Full size table

Mesenchymal stromal cells were isolated from bone biopsies obtained from the iliac crest and were collected in V-shaped glass tube and extensively minced with surgical scissors. The supernatants were collected, and the MSCs were isolated using a Ficoll–Hypaque density gradient (Pharmacia Biotech, Uppsala, Sweden). After 1 week, the nonadherent cells were removed and the adherent cells were analyzed at different passages (p1–p3). OB cells were directly isolated from the minced bone chips as described earlier.6 The chips were digested using 1 mg/ml collagenase P (Boehringer Mannheim Corporation, Indianapolis, IN, USA) at 37 °C for 2 h under rotation, washed and placed in 100 × 20 mm dishes in Dulbecco's modified Eagle's medium/Ham's F12K without a calcium-supplemented medium (Gibco, Invitrogen, Scotland, UK) and then fed with a complete medium twice a week. After 2 weeks the chips were removed and the OBs were allowed to grow until confluence and analyzed at different passages.

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Acknowledgements

This study was supported by grants from Regione Emilia-Romagna (NG, VR), Associazione Italiana Ricerca sul Cancro (AIRC) (NG, AN), the International Myeloma Foundation Award 2009 (NG) and a fellowship from Fondazione Italiana Ricerca sul Cancro (FIRC) (LA).

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Authors and Affiliations

  1. Department of Internal Medicine and Biomedical Science, Hematology and BMT, University of Parma, Parma, Italy

    N Giuliani, P Storti, G Sammarelli, S Colla, M Abeltino, M Bolzoni & V Rizzoli

  2. SC Laboratorio di Immunoreumatologia e Rigenerazione Tissutale, Istituto Ortopedico Rizzoli, Bologna, Italy

    G Lisignoli, C Manferdini & E Gabusi

  3. Dipartimento di Patologia Umana ed Ereditaria, Sezione Biologia generale e Genetica Medica, University of Pavia, Pavia, Italy

    F Novara & O Zuffardi

  4. Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy

    N Zaffaroni & R Villa

  5. Department of Medical Sciences, Hematology 1-CTMO ‘Fondazione IRCCS Policlinico’, University of Milan, Milan, Italy

    L Agnelli, K Todoerti & A Neri

  6. Oncoematologia Pediatrica, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

    M E Bernardo

  7. Cattedra di Ematologia, Università di Torino, Torino, Italy

    A Rocci & A Palumbo

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  1. N Giuliani
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  2. G Lisignoli
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Correspondence to N Giuliani.

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Giuliani, N., Lisignoli, G., Novara, F. et al. Bone osteoblastic and mesenchymal stromal cells lack primarily tumoral features in multiple myeloma patients. Leukemia 24, 1368–1370 (2010). https://doi.org/10.1038/leu.2010.96

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