CXCL7-Mediated Stimulation of Lymphangiogenic Factors VEGF-C, VEGF-D in Human Breast Cancer Cells

Abstract EN

Increased expression of lymphangiogenesis factors VEGF-C/D and heparanase has been correlated with the invasion of cancer.

Furthermore, chemokines may modify matrix to facilitate metastasis, and they are associated with VEGF-C and heparanase.

The chemokine CXCL7 binds heparin and the G-protein-linked receptor CXCR2.

We investigated the effect of CXCR2 blockade on the expression of VEGF-C/D, heparanase, and on invasion.

CXCL7 siRNA and a specific antagonist of CXCR2 (SB225002) were used to treat CXCL7 stably transfected MCF10AT cells.

Matrigel invasion assays were performed.

VEGF-C/D expression and secretion were determined by real-time PCR and ELISA assay, and heparanase activity was quantified by ELISA.

SB225002 blocked VEGF-C/D expression and secretion (P<.01).

CXCL7 siRNA knockdown decreased heparanase (P<.01).

Both SB225002 and CXCL7 siRNA reduced the Matrigel invasion (P<.01).

The MAP kinase signaling pathway was not involved.

The CXCL7/CXCR2 axis is important for cell invasion and the expression of VEGF-C/D and heparanase, all linked to invasion.