Anti-prokineticin1 (PROK1) monoclonal antibody suppresses angiogenesis and tumor growth in colorectal cancer.
BACKGROUND
The prokineticin1 (PROK1) gene has been cloned as an angiogenic growth factor from endocrine gland cells. However, we have not known about potentials of anti-PROK1 monoclonal antibody in human cancers. Here we investigated how the anti-PROK1 monoclonal antibody (mAb; established by our department) would affect the high-PROK1-expressing colorectal cancer (CRC) cells in vitro and vivo.


METHODS
We confirmed PROK1 protein expression in the CRC cells by performing immunohistochemical staining and measured the amount of soluble PROK1 protein. Next, we mixed the CRC cell culture fluid with the anti-PROK1mAb to examine angiogenic activity in vitro and in vivo. Additionally, we investigated whether the anti-PROK1mAb would affect the tumor-forming capability of high PROK1-expressing CRC cells implanted into mice.


RESULTS
PROK1 protein expression was confirmed in 3 CRC cell lines, and soluble PROK1 protein was also confirmed in the CRC cell culture fluid. The culture fluid increased angiogenesis in vitro and vivo, whereas the anti-PROK1mAb suppressed angiogenesis. Subcutaneous tumor formation and tumor angiogenesis in mice were suppressed by the anti-PROK1mAb treatment. The anti-PROK1mAb significantly suppressed the number of CD31 stained cells in mice.


CONCLUSIONS
The in vitro and vivo experimental system indicated that the anti-PROK1mAb could suppress angiogenesis and tumor growth in the CRC strains.
First Department of Surgery, University of Fukui, Eiheiji, Fukui, Japan, tgoi@u-fukui.ac.jp.
Takanori
T
Goi
Toshiyuki
T
Nakazawa
Yasuo
Y
Hirono
Akio
A
Yamaguchi
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D017077:Culture Media, Conditioned / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D005768:Gastrointestinal Hormones / Q000032:analysis / Q000276:immunology*; D045325:HCT116 Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D042662:Vascular Endothelial Growth Factor, Endocrine-Gland-Derived / Q000032:analysis / Q000276:immunology*
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D017077:Culture Media, Conditioned; D005768:Gastrointestinal Hormones; C467610:PROK1 protein, human; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D042662:Vascular Endothelial Growth Factor, Endocrine-Gland-Derived