Chemokine CXCL14 is a multistep tumor suppressor

Abstract Background The multi-step nature of cancer that involves carcinogenesis, an increase in tumor size, and invasion and/or metastasis is well recognized. These respective steps depend on the mutation of several genes, epigenetic changes in cells, and interactions between cancer cells and other cells in the microenvironment. To identify novel intercellular tumor suppressors, we screened for genes whose expression was down-regulated in oral cancer cells. Highlight The chemokine, CXCL14, was down-regulated in oral carcinoma cells, and its up-regulation suppressed tumor cell growth in vivo , indicating that CXCL14 is a tumor growth suppressor. Moreover, to investigate whether CXCL14 suppresses tumors originating from the other cells in a paracrine or endocrine fashion, we generated CXCL14 transgenic (Tg) mice. The Tg mice exhibited a suppressed rate of carcinogenesis, decreased volume of transplanted tumors, and reduced pulmonary metastasis, as well as an increased survival rate following tumor cell injection, compared with wild-type mice. The CXCL14­expressing Tg mice showed no apparent abnormality when observed up to 2 years of age, and, interestingly, in a normal human population an individual was found to have a blood level of CXCL14 protein 10-fold higher than the average but did not present any apparent abnormalities. Conclusion These data indicate that CXCL14 expressed at high levels does not have severe side effects, and, thus, we propose CXCL14 as a promising molecular target for cancer suppression/prevention.