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Prepublished online as a Blood First Edition Paper on June 7, 2002; DOI 10.1182/blood-2002-01-0030.
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Blood, 1 October 2002, Vol. 100, No. 7, pp. 2578-2585
NEOPLASIA
Characterization of hyaluronan synthase expression and hyaluronan
synthesis in bone marrow mesenchymal progenitor cells: predominant
expression of HAS1 mRNA and up-regulated hyaluronan synthesis in bone
marrow cells derived from multiple myeloma patients
Anthony Calabro,
Martin M. Oken,
Vincent C. Hascall, and
Anna M. Masellis
From the Virginia Piper Cancer Institute, Abbott
Northwestern Hospital, Minneapolis, MN; and Department of Biomedical
Engineering, Lerner Research Institute, The Cleveland Clinic
Foundation, OH.
Hyaluronan (HA) is suggested to play a role in the pathophysiology
of multiple myeloma. To further investigate the role of HA in this
disease, we examined hyaluronan synthase (Has) gene expression and HA
production in bone marrow mesenchymal progenitor cells (bmMPCs) derived
from multiple myeloma patients. The relative abundance of mRNA for each
HAS gene was determined using competitive reverse
transcription-polymerase chain reaction (cRT-PCR), whereas HA
production was detected by fluorophore-assisted carbohydrate electrophoresis (FACE). We determined the basal expression of Has
isoforms in myeloma bmMPCs and then compared this expression with
expression in healthy donor bmMPCs. Of the 3 Has isoforms, Has1 mRNA was expressed predominantly in myeloma bmMPCs, with expression 7.6-fold greater than Has2. Compared with normal bmMPCs, Has1 mRNA expression was 20-fold greater in myeloma bmMPCs. Normal bmMPCs predominantly expressed Has2 mRNA (8.2-fold greater than myeloma
bmMPCs). Upon coculture of myeloma bmMPCs with plasma cells, Has1
transcript was strongly attenuated. FACE results show that myeloma
bmMPCs synthesize 5.7-fold more HA than those from healthy
donors. These data suggest that myeloma bmMPCs could be an important
component of the myeloma pathophysiology in vivo by their increased
expression of extracellular matrix (ECM) components relevant to plasma
cell growth and survival.

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