Endocrine gland-derived vascular
endothelial growth factor (EG-VEGF) has recently been identified as one of the vascular
endothelial growth factors, and it is considered that the overexpression of
EG-VEGF in colon cancer is related to hepatic metastasis. In this study, we
report our recent novel findings of the involvement of EG-VEGF in cell invasion of
colon cancer cells. Colon cancer cell lines (DLD-1 and HCT116) with high
expression of prokineticin receptor (PK-R) 1 and 2 were stimulated with the EG-VEGF
protein. Furthermore, Matrigel cell invasion assay was performed to examine the
changes in cancer cell invasion. In addition, we investigated the mRNA
expression of matrix metalloproteinase (MMP)-2, -7 and -9 in cancer cells.
Finally, the EG-VEGF receptor on the colon cancer cell membrane was blocked by
anti-PK-R1 and -PK-R2 antibodies to study whether cell invasion ability would be
altered. In colon cancer cell lines where the expression of PK-R1 and 2 was
confirmed, stimulation with EG-VEGF increased cell invasion a maximum of ~3-5 times.
Furthermore, an increase in the mRNA and protein expression of MMP-2, -7 and -9 was
observed. We also observed that the cell invasion rate decreased only after
exposure to the anti-PK-R2 antibody. The study showed that the EG-VEGF protein may
act on MMP-2, -7 and -9 via PK-R2 to strengthen cell invasion ability in colon
cancer cell lines. |