Characterization of bone marrow stromal cells from multiple myeloma

Maria Grazia Gregoretti, Daniela Gottardi, Paolo Ghia, Luciana Bergui, Franca Merico, Pier Carlo Marchisio, Federico Caligaris-Cappio

Research output: Contribution to journalArticlepeer-review

Abstract

We have cultured multiple myeloma (MM) bone marrow (BM) stromal cells that are able to sustain the in vitro growth of monoclonal B-cells. Our aim was to evaluate which adhesion molecules are expressed and which extracellular matrix proteins are produced by these cells and whether they differ from the stromal cells that can be grown under the same experimental conditions from the BM of monoclonal gammopathies of undetermined significance (MGUS) and of normal donors. MM BM stromal cells that support malignant B-cell development have a striking proliferative ability that is absent in MGUS and normal donors of the same age group and are formed by four major different cell populations. Two kinds of HLA-DR+, CD10+ fibroblast-like cells can be recognized through the expression (or the lack) of α-smooth muscle actin isoform; further, macrophages and osteoclasts can be identified. Fibroblast-like cells that express α-smooth muscle actin isoform, often organized along stress fibers in a periodic fashion, may be considered as myofibroblasts. Fibroblast-like cells react strongly with antibodies to CD54 (ICAM-1), integrin β1, β3, β5 and some of associated α chains. Integrin β1 is diffusely exposed on the surface while β3 is clustered in focal contacts in association with vinculin. A still undetermined subpopulation of fibroblasts is highly positive for ανβ5 that is clustered at focal contacts as shown by association with stress fiber termini and by interference reflection microscopy. A major difference between MM and normal donor BM stromal cells involves lower deposition and simpler organization of the extracellular matrix proteins (fibronectin, laminin, collagen type IV) deposited by MM fibroblast-like cells. CD14+ macrophages from MM, MGUS and normal donor BM are CD11a+ (αL), CD11b+ (αM), CD11c+ (αX), CD54+ (ICAM-1), CD56+ (N-CAM), β1 and β2 (CD18) integrin positive. The integrin β1 is diffusely expressed on the surface, while β2 is concentrated in podosomes. MM osteoclasts show a weak diffuse staining with CD54 and CD56 MoAbs; β1 integrin has a diffuse surface expression, while β3 integrin is concentrated in the podosomes. Normal donor osteoclasts are CD54- and the staining with CD56 is barely visible. These findings lead us to suggest that the microenvironment provided by MM BM may be significantly different from that of normal BM indicating its potential role in controlling the local proliferation and differentiation of malignant B-lineage cells.

Original languageEnglish
Pages (from-to)675-682
Number of pages8
JournalLeukemia Research
Volume18
Issue number9
DOIs
Publication statusPublished - 1994

Keywords

  • adhesion molecules
  • Bone marrow
  • cultures
  • integrins
  • myeloma
  • stromal cells

ASJC Scopus subject areas

  • Cancer Research
  • Hematology
  • Oncology

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