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Blood, 1 August 2001, Vol. 98, No. 3, pp. 771-780
NEOPLASIA
Identifying intercellular signaling genes expressed in malignant
plasma cells by using complementary DNA arrays
John De Vos,
Guilhem Couderc,
Karin Tarte,
Michel Jourdan,
Guilhem Requirand,
Marie-Claude Delteil,
Jean-François Rossi,
Nadir Mechti, and
Bernard Klein
From INSERM U475, Unit for Cellular Therapy, and
Service d'Hématologie et d'Oncologie Médicale,
CHU Montpellier, France.
In multiple myeloma (MM), the growth of primary plasma cells
depends not only on interleukin-6 (IL-6), but also on additional unidentified signals delivered by the bone marrow environment. Using
Atlas complementary DNA (cDNA) arrays comprising 268 genes coding for
intercellular signaling molecules, this study identified genes that are
overexpressed in myeloma cells compared to autologous B-lymphoblastoid
cell lines. These genes encode the oncogenic Tyro3 tyrosine kinase
receptor, the heparin-binding epidermal growth factor-like growth
factor (HB-EGF) that is an epithelial autocrine tumor growth factor,
the thrombin receptor (TR) that is linked to HB-EGF and syndecan-1
processing and to cell invasion, chemokine receptors CCR1 and CCR2, the
Wnt pathway actor Frizzled-related protein (FRZB), and the
Notch receptor ligand Jagged 2. These data, obtained with the Atlas
cDNA array, were confirmed by reverse transcriptase-polymerase chain
reaction or protein analysis or both. Furthermore, Tyro3,
HB-EGF, TR, and FRZB gene
expression was documented in purified primary malignant plasma cells
from patients with plasma cell leukemia or MM. HB-EGF and FRZB were poorly expressed in purified polyclonal plasma cells. Finally, HB-EGF
was proved to be an essential autocrine growth factor for the XG-1
myeloma cells. This study shows the potency and the biologic relevance
of cDNA arrays used to analyze simultaneously a large panel of
intercellular signaling genes and, by identifying several genes
overexpressed in malignant plasma cells, opens new fields of
investigation in MM biology.
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