PIGF antagonizes VEGF induced angiogenesis - tumor growth

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PIGF antagonizes VEGF induced angiogenesis - tumor growth

Postby patoco » Fri Sep 22, 2006 10:28 am

Placenta growth factor-1 antagonizes VEGF-induced angiogenesis and tumor growth by the formation of functionally inactive PlGF-1/VEGF heterodimers.

Eriksson A, Cao R, Pawliuk R, Berg SM, Tsang M, Zhou D, Fleet C,
Tritsaris K, Dissing S, Leboulch P, Cao Y.

Microbiology and Tumor Biology Center, Karolinska Institute, S-171 77,
Stockholm, Sweden.

Tumor growth and metastasis require concomitant growth of new blood
vessels, which are stimulated by angiogenic factors, including vascular
endothelial growth factor (VEGF), secreted by most tumors. Whereas the
angiogenic property and molecular mechanisms of VEGF have been well
studied, the biological function of its related homolog, placenta
growth factor (PlGF), is poorly understood. Here we demonstrate that
PlGF-1, an alternatively spliced isoform of the PlGF gene, antagonizes
VEGF-induced angiogenesis when both factors are coexpressed in murine
fibrosarcoma cells.

Overexpression of PlGF-1 in VEGF-producing tumor
cells results in the formation of PlGF-1/VEGF heterodimers and
depletion of the majority of mouse VEGF homodimers. The heterodimeric
form of PlGF-1/VEGF lacks the ability to induce angiogenesis in vitro
and in vivo. Similarly, PlGF-1/VEGF fails to activate the
VEGFR-2-mediated signaling pathways.

Further, PlGF-1 inhibits the growth of a murine fibrosarcoma by approximately 90% when PlGF-1-expressing tumor cells are implanted in syngeneic mice. In contrast, overexpression of human VEGF in murine tumor cells causes accelerated and exponential growth of primary fibrosarcomas and early hepatic metastases. Our data demonstrate that PlGF-1, a member of the VEGF family, acts as a natural antagonist of VEGF when both factors are synthesized in the same population of cells. The underlying mechanism is due to the formation of functionally inactive heterodimers.

PMID: 12086892 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/quer ... med_docsum

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