Title

Vascular endothelial growth factor is an autocrine survival factor for neuropilin-expressing breast carcinoma cells

UMMS Affiliation

Department of Cancer Biology

Date

8-2-2001

Document Type

Article

Subjects

1-Phosphatidylinositol 3-Kinase; Apoptosis; Breast Neoplasms; Cell Hypoxia; Cell Survival; Chromones; Endothelial Growth Factors; Enzyme Activation; Enzyme Inhibitors; Humans; Lymphokines; Morpholines; Nerve Tissue Proteins; Neuropilin-1; Signal Transduction; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

Abstract

We identify a novel function for the vascular endothelial growth factor (VEGF) in its ability to stimulate an autocrine signaling pathway in metastatic breast carcinoma cells that is essential for their survival. Suppression of VEGF expression in metastatic cells in vitro induced their apoptosis, in addition to inhibiting the constitutively elevated phosphatidylinositol 3'-kinase activity that is characteristic of these cells and important for their survival. Hypoxia enhanced the survival of metastatic cells by increasing VEGF expression. The importance of the VEGF receptor neuropilin was indicated by the ability of a neuropilin-binding VEGF isoform to enhance breast carcinoma survival. Moreover, the expression of neuropilin in neuropilin-deficient breast carcinoma cells protected them from apoptosis. The identification of this VEGF autocrine signaling pathway has important implications for tumor metastasis and therapeutic intervention.

Rights and Permissions

Citation: Cancer Res. 2001 Aug 1;61(15):5736-40.

Related Resources

Link to Article in PubMed

PubMed ID

11479209