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.