Endocrine gland-derived vascular endothelial growth factor strengthens cell invasion ability via prokineticin receptor 2 in colon cancer cell lines

• DOI: 10.3892/or.2012.2124
• Publication Date: 2012-11-06T06:31:27Z
• Authors: SHINSUKE TABATA; TAKANORI GOI; TOSHIYUKI NAKAZAWA; YOUHEI KIMURA; KANJI KATAYAMA; KIO YAMAGUCHI
• Keywords: Receptors, Peptide; Gene Expression; HCT116 Cells; Antibodies; Receptors, G-Protein-Coupled; 3. Good health; Gastrointestinal Hormones; 03 medical and health sciences; 0302 clinical medicine; Matrix Metalloproteinase 9; Cell Movement; Matrix Metalloproteinase 7; Colonic Neoplasms; Humans; Matrix Metalloproteinase 2; Neoplasm Invasiveness; Vascular Endothelial Growth Factor, Endocrine-Gland-Derived; RNA, Messenger

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.