Dual effects of IGFBP‐3 on endothelial cell apoptosis and survival: Involvement of the sphingolipid signaling pathways

@article{Granata2004DualEO,
  title={Dual effects of IGFBP‐3 on endothelial cell apoptosis and survival: Involvement of the sphingolipid signaling pathways},
  author={Riccarda Granata and Letizia Trovato and Giovanni Garbarino and Marina Taliano and Renata Ponti and Giusy Sala and Riccardo Ghidoni and Ezio Ghigo},
  journal={The FASEB Journal},
  year={2004},
  volume={18}
}
Insulin‐like growth factor binding protein (IGFBP)‐3 has both growth‐inhibiting and growth‐promoting effects at the cellular level. The cytotoxic action of several anticancer drugs is linked to increased ceramide generation through sphingomyelin hydrolysis or de novo biosynthesis. Herein, we investigated the role of IGFBP‐3 on apoptosis of human umbilical vein endothelial cells (HUVEC) and its relationship with ceramide levels. We report that IGFBP‐3 exerts dual effects on HUVEC, potentiating… 
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References

SHOWING 1-10 OF 71 REFERENCES
Insulin-like growth factor binding protein-3 mediates serum starvation- and doxorubicin-induced apoptosis in H9c2 cardiac cells
TLDR
Findings indicate that IGFBP-3 could play proapoptotic action at the myocardial level and suggest a novel role for this protein in cardiovascular dysfunction.
Resveratrol induces growth inhibition and apoptosis in metastatic breast cancer cells via de novo ceramide signaling
TLDR
It is shown that resveratrol can induce growth inhibition and apoptosis in MDA‐MB‐231, a highly invasive and metastatic breast cancer cell line, in concomitance with a dramatic endogenous increase of growth inhibitory/proapoptotic ceramide.
Rapid insulin-like growth factor (IGF)-independent effects of IGF binding protein-3 on endothelial cell survival.
TLDR
The antiproliferative and proapoptotic effects of exogenous IGFBP-3 upon VEGF-induced HUVEC survival were not inhibited by blockade of the type 1 IGF receptor with alpha IR-3 immunoglobulin, which fully prevented IGF actions.
Insulin-like Growth Factor-binding Protein (IGFBP-3) Predisposes Breast Cancer Cells to Programmed Cell Death in a Non-IGF-dependent Manner*
TLDR
It is found that IGFBP-3 had no direct inhibitory effect on Hs578T cells but could accentuate apoptosis induced by the physiological trigger ceramide in an IGF-independent manner.
Cellular growth inhibition by IGFBP‐3 and TGF‐β1 requires LRP‐1
TLDR
The results suggest that the LRP‐1/TβR‐V/IGFBP‐3 receptor is required for the growth inhibitory response to IGF BP‐3 and TGF‐β1.
Enhanced expression of insulin-like growth factor binding protein-3 sensitizes the growth inhibitory effect of anticancer drugs in gastric cancer cells.
IGF-1 regulates migration and angiogenesis of human endothelial cells.
TLDR
Examination of the effects of high glucose and/or IGF-1 on cell migration and angiogenesis by using human endothelial cells (EC) in vitro indicates that hyperglycemia and IGF-0, respectively, stimulate the EC migration, and tubular formation is induced by a combination of IGF- 1 and hyperglyCEmia.
Differential interactions between IGFBP-3 and transforming growth factor-beta (TGF-β) in normal vs cancerous breast epithelial cells
TLDR
Insulin-like growth factor-binding protein-3 has intrinsic activity capable of inhibiting or enhancing the growth and survival of breast epithelial cells depending on the cell line and exposure to other cytokines.
Insulin-like Growth Factor (IGF)-binding Protein-3 Induces Apoptosis and Mediates the Effects of Transforming Growth Factor-β1 on Programmed Cell Death through a p53- and IGF-independent Mechanism*
TLDR
It is suggested that IGFBP-3 induces apoptosis through a novel pathway independent of either p53 or the IGF·IGF receptor-mediated cell survival pathway and that IGF BP-3 mediates TGF-β1 induced apoptosis in PC-3 cells.
Role of PI 3-kinase in angiopoietin-1-mediated migration and attachment-dependent survival of endothelial cells.
TLDR
It is shown that PI 3-kinase-dependent activation of Akt and attachment to extracellular matrix are required for angiopoietin-1-mediated endothelial cell survival and that PI3-kinases lipid products are key mediators of the biological effects of angiopOietIn-1.
...
...