Inhibitory effect of an anti-prokineticin-1 antibody on liver metastasis in mice injected with human colorectal cancer cell lines

Abstract

Controlling hematogenous metastases is an effective treatment strategy for colorectal cancer. Multidisciplinary treatment for colorectal cancer has made great strides, and molecularly-targeted drugs have greatly improved the prognosis of patients. However, currently accepted molecularly- targeted therapeutic agents require concomitant use with anticancer agents. Thus, new molecularly-targeted drugs need to be developed. The prokineticin family of angiogenic factors has the potential of becoming target molecules. Among them, prokineticin-1 (PROK1) is involved in the promotion of angiogenesis, tumor growth, and liver metastases in colorectal cancer. We manufactured our own anti-PROK1 antibody and verified its effect in inhibiting liver metastases and prolonging survival. The method involved creating liver metastasis model mice using human colorectal cancer cell lines. These mice were divided into anti-PROK1 antibody administration and control groups. Mice were treated intraperitoneally with antibodies or phosphate-buffered saline (control) every 3 days. The number of liver metastatic lesions and survival time of each group were compared. The number of metastatic lesions decreased, and survival time was significantly prolonged in the antibody-treated group. Furthermore, using microarray and immunostaining in both groups, we confirmed the effect of administering the anti-PROK1 antibody on the oxidation, reduction, and apoptotic processes, and cell division of tumors, and that alterations were suppressed in 72.1% of the genes examined. The expression of transforming growth factor-{beta} (TGF-{beta}), a tumor suppressor gene, was increased. The increased expression of TGF-{beta} via PROK1 antibody administration may suppress the cancer cell proliferation ability, leading to liver metastasis suppression and prolonging the survival time of mice.