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Etiology and Pathogenesis
> Cancer
Stem Cells
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Cancer Research 66, 8042-8048, August 15, 2006
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Abstract |
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Autocrine/Paracrine Platelet-Derived
Growth Factor Regulates Proliferation of Neural Progenitor Cells
Anna Erlandsson1,
Karin Brännvall1,
Sigrun Gustafsdottir2,
Bengt Westermark2
and Karin Forsberg-Nilsson1
1Department of Medical
Biochemistry and Microbiology, Uppsala University; and
Department of Genetics and Pathology, Uppsala University, Rudbeck
Laboratory, Uppsala, Sweden. -- Requests for reprints: Karin Forsberg-Nilsson,
Department of Medical Biochemistry and Microbiology, Uppsala
University, Box 582, 751 23 Uppsala, Sweden. Phone: 46-18-471-41-58;
Fax: 46-18-471-42-44; E-mail: karin.nilsson@imbim.uu.se.
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Growth factors play an important role in
regulating neural stem cell proliferation and
differentiation.
This study shows that platelet-derived growth factor (PDGF)
induces a partial differentiation of neural stem/progenitor
cells (NSPCs) in the absence of other mitogens in vitro.
NSPCs thus acquire an immature morphology and display
markers for both neurons and glia.
In addition, these cells do not readily mature in the
absence of further stimuli.
When NSPC cultures treated with PDGF were exposed to additional
differentiation factors, however, the differentiation proceeded
into neurons, astrocytes, and oligodendrocytes.
We find that NSPC cultures are endowed with an endogenous
PDGF-BB production.
The PDGF-BB expression peaks during early differentiation and
is present both in cell lysates and in conditioned medium, allowing
for autocrine as well as paracrine signaling.
When the NSPC-derived PDGF was inhibited, progenitor cell
numbers decreased, showing that PDGF is involved in NSPC
expansion.
Addition of a PDGF receptor (PDGFR) inhibitor resulted in a more
rapid differentiation.
Neurons and oligodendrocytes appeared earlier and had more
elaborate processes than in control cultures where
endogenous PDGFR signaling was not blocked.
Our observations point to PDGF as an inducer of partial
differentiation of NSPC that also sustains progenitor cell
division.
Such an intermediate stage in stem cell differentiation is
of relevance for the understanding of brain tumor
development because autocrine PDGF stimulation is believed
to drive malignant conversion of central nervous system
progenitor cells.
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© 2006 American Association for Cancer Research
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Abstract
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