Possible roles of CXCL17 in angiogenesis during tumor progression

Abstract

Recently, chemokines have drawn more attention as important targets in cancer therapy from viewpoints of tumor metastasis and recruitment of immune suppressor cells. Our previous studies showed that CXCL17 expression by tumor cells enhanced the tumor growth in mice, and demonstrated that CXCL17 also induced migration of myeloid‐derived suppressor cells (MDSCs) into the tumors. In the present study, we focused on tumor blood vessels as one of responsible factors in the progression of CXCL17‐expressing tumors to clarify the effects of CXCL17 and neutrophil‐like MDSCs on tumor blood vessels. CXCL17‐expressing colon26cells (a mouse colon cancer cell line) injected subcutaneously into BALB/c mice, showed an increase in CD31+ endothelial cell areas and well‐maintained blood vessel meshworks compared with CXCL17‐nonexpressing control tumors. Moreover, the number of NG2+ pericytes increased in the tumor vessels of these CXCL17‐expressing tumors. Furthermore, CXCL17 was adopted in the chemotaxis assay to separate the neutrophil‐like MDSCs from mouse splenocytes. Tumor cells transplanted together with the CXCL17‐chemotactic neutrophil‐like MDSCs enhanced their tumor angiogenesis compared with these transplanted with irrelevant splenocytes. These results suggest that CXCL17 may induce the structural and functional changes in tumor blood vessels via controlling neutrophil‐like MDSCs.