Title

Vascular endothelial growth factor promotes breast carcinoma invasion in an autocrine manner by regulating the chemokine receptor CXCR4

UMMS Affiliation

Department of Cancer Biology

Date

12-25-2002

Document Type

Article

Subjects

3T3 Cells; Animals; Antibodies; Breast Neoplasms; Cell Movement; Cell Survival; Chemokine CXCL12; Chemokines, CXC; Culture Media, Conditioned; Endothelial Growth Factors; Heterotrimeric GTP-Binding Proteins; Humans; Intercellular Signaling Peptides and Proteins; Lymphokines; Mice; Neoplasm Invasiveness; Neuropilin-1; Oligopeptides; Receptors, CXCR4; Signal Transduction; Tumor Cells, Cultured; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

Abstract

We report that vascular endothelial growth factor (VEGF), a major angiogenic factor, is also arequisite autocrine factor for breast carcinoma invasion in vitro and that the VEGF receptor Neuropilin-1 but not Flt-1 is essential for this function. VEGF regulates expression of the chemokine receptor CXCR4, and this VEGF target is needed for invasion but not for cell survival. CXCR4 mediates migration of breast carcinoma cells toward stromal-derived factor-1, and this migration is dependent on autocrine VEGF. Of interest, a CXCR4-inhibitory peptide that is currently in HIV clinical trials suppressed invasion. Our findings indicate that a VEGF autocrine pathway induces chemokine receptor expression in breast carcinoma cells, thus promoting their directed migration toward specific chemokines.

Rights and Permissions

Citation: Cancer Res. 2002 Dec 15;62(24):7203-6.

Related Resources

Link to Article in PubMed

PubMed ID

12499259