A Novel Binding Protein for Fibroblast Growth Factors (FGF-BP2):Cloning, Expression Profile, Tumorigenic Activity and Regulation of Gene Expression by Fetal Bovine Serum and Retinoic Acid.
Angiogenesis is one of the essential alterations in cell physiology that dictate malignant growth and metastasis and has long been a major focus in molecular cancer research. More than a dozen distinct proteins are currently known to induce proliferation of endothelial cells in vitro...
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|Summary:||Angiogenesis is one of the essential alterations
in cell physiology that dictate malignant growth and metastasis
and has long been a major focus in molecular cancer research.
More than a dozen distinct proteins are currently known to
induce proliferation of endothelial cells in vitro and/or
angiogenesis in vivo. Some of the most effective and
best-studied angiogenic factors are fibroblast growth factors
(FGFs) that are potent stimulators of new blood vessel
formation during tumor growth. However, some FGFs (aFGF and
bFGF) are upon secretion immobilized in the extracellular
matrix (ECM) and unable to reach their high affinity receptors.
There are several possible mechanisms by which bFGF can be
released from its matrix storage site and thus activated. One
established mechanism is the action of an FGF binding protein
(FGF-BP1). FGF-BP1 activates bFGF and is thus able to stimulate
tumor cell proliferation and angiogenesis. Recently a human
cDNA clone containing an open reading frame for a protein,
which shows amino acid sequence similarity of 21% and homology
of 41 % to FGF-BP1 was discovered. This novel molecule was
In this study the FGF-BP2 expression profile
under physiological conditions in normal human tissue and in
the pathological setting of tumor cell lines was evaluated by
Northern Blotting analysis. Following its in vitro gene
regulation by various drugs and growth factors was studied.
Finally the FGF-BP2 cDNA was cloned into an expression vector,
the gene was overexpressed in the human adrenal carcinoma cell
line SW-13 and then analyzed for its tumorigenic potential in
soft agar growth assays.
This study revealed a widespread
FGF-BP2 mRNA expression in normal human tissue. Among 36 tumor
cell lines tested though, FGF-BP2 mRNA expression was limited
to all of the melanoma cell lines. Interestingly, no FGF-BP2
mRNA expression was detected in normal human neonatal
melanocytes. Furthermore it was evaluated if some of the well
defined mechanisms for gene regulation that are known for
FGF-BP1 also exist for FGF-BP2 as tested in two melanoma cell
lines. However, in contrast to what is known for FGF-BP1 it was
neither possible to show a significant up-regulation of the
FGF-BP2 mRNA expression by Fetal Bovine Serum, EGF and TPA, nor
was any down-regulation inducible by all-trans retinoic acid.
Finally it was shown that FGF-BP2 overexpression in the human
adrenal carcinoma cell line SW-13 promotes a bFGF-dependent
colony formation in vitro, indicating its tumorigenic
This study demonstrates that the novel FGF-binding
protein has not only structural but also functional
similarities to FGF-BP1. Its biological activity, together with
other data that are not presented here suggest that FGF-BP2 is
like FGF-BP1 a tumor promoting agent that may solubilize matrix
bound bFGF. However, FGF-BP2 shows a different expression
pattern from FGF-BP1 and does not seem to follow similar
mechanisms of transcriptional or posttranscriptional gene
regulation. Most interesting though seems to be the function
that FGF-BP2 might have in melanoma progression since it is
known that bFGF and its activated signal pathway play a crucial
role in the development of melanoma.|
|Physical Description:||117 Pages|