Placenta growth factor is a survival factor for human malignant mesothelioma cells.
2009
Placenta growth factor (PlGF) is a key regulator of pathological
angiogenesis and its overexpression has been linked to neoplastic
progression. To assess whether PlGF could have a role in malignant
mesothelioma (MM), we analyzed the expression of PlGF, VEGF, and
their cognate receptors (VEGF-R1 and VEGF-R2) and coreceptors
(neuropilin-1 and neuropilin-2) in MM cell lines as well as in resected
MM tissues, hyperplastic/reactive mesothelium and normal
mesothelium. MM cell cultures expressed both ligands and the associated
receptors to a variable extent and released different amounts of PlGF. As
assessed by immunohistochemistry, PlGF expression was switched on in
hyperplastic/reactive compared to normal mesothelium. Moreover, 74
and 94% of MM tissues overexpressed PlGF and VEGF-R1, respectively
(p<0.05). Administration of recombinant PlGF-2 did not elicit a
significant stimulation of MM cell growth, while it was associated with
a transient phosphorylation of Akt, suggesting that PlGF-2 could activate
downstream effectors of cytoprotective and anti-apototic signals via
VEGF-R1 in MM cells. Indeed, the administration of an anti-PlGF
antibody was found to cause a significant reduction of MM cell survival.
In conclusion, our data demonstrate that, by acting as a survival factor,
PlGF can play a role which goes beyond the stimulation of angiogenesis
in MM. This evidence could help the rational design of new therapeutic
interventions for this aggressive tumor.
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