Goi Takanori, Nakazawa Toshiyuki, Hirono Yasuo, Yamaguchi Akio
First Department of Surgery, University of Fukui, Eiheiji, Fukui, Japan,
Ann Surg Oncol. 2014 Dec;21 Suppl 4:S665-71. doi: 10.1245/s10434-014-3765-8. Epub 2014 May 17.
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.
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.
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.
The in vitro and vivo experimental system indicated that the anti-PROK1mAb could suppress angiogenesis and tumor growth in the CRC strains.
促动力蛋白1（PROK1）基因已作为一种血管生成生长因子从内分泌腺细胞中克隆出来。然而，我们对抗PROK1单克隆抗体在人类癌症中的潜力尚不清楚。在此，我们研究了抗PROK1单克隆抗体（由我们科室制备）在体外和体内对高表达PROK1的结直肠癌（CRC）细胞的影响。
我们通过免疫组织化学染色确认CRC细胞中PROK1蛋白的表达，并测量可溶性PROK1蛋白的量。接下来，我们将CRC细胞培养液与抗PROK1单克隆抗体混合，以检测体外和体内的血管生成活性。此外，我们研究了抗PROK1单克隆抗体是否会影响植入小鼠体内的高表达PROK1的CRC细胞的肿瘤形成能力。
在3种CRC细胞系中确认了PROK1蛋白的表达，并且在CRC细胞培养液中也确认了可溶性PROK1蛋白。培养液在体外和体内均可促进血管生成，而抗PROK1单克隆抗体则抑制血管生成。抗PROK1单克隆抗体处理可抑制小鼠皮下肿瘤形成和肿瘤血管生成。抗PROK1单克隆抗体显著抑制了小鼠中CD31染色细胞的数量。
体外和体内实验系统表明，抗PROK1单克隆抗体可抑制CRC细胞系中的血管生成和肿瘤生长。
