CXCL17 Expression by Tumor Cells Recruits CD11b⁺Gr1^highF4/80⁻ Cells and Promotes Tumor Progression

<div><h3>Background</h3><p>Chemokines are involved in multiple aspects of pathogenesis and cellular trafficking in tumorigenesis. In this study, we report that the latest member of the C-X-C-type chemokines, CXCL17 (DMC/VCC-1), recruits immature myeloid-derived cells and enhances early tumor progression.</p> <h3>Methodology/Principal Findings</h3><p>CXCL17 was preferentially expressed in some aggressive types of gastrointestinal, breast, and lung cancer cells. CXCL17 expression did not impart NIH3T3 cells with oncogenic potential <em>in vitro</em>, but CXCL17-expressing NIH3T3 cells could form vasculature-rich tumors in immunodeficient mice. Our data showed that CXCL17-expressing tumor cells increased immature CD11b⁺Gr1⁺ myeloid-derived cells at tumor sites in mice and promoted CD31⁺ tumor angiogenesis. Extensive chemotactic assays proved that CXCL17-responding cells were CD11b⁺Gr1^highF4/80⁻ cells (∼90%) with a neutrophil-like morphology <em>in vitro</em>. Although CXCL17 expression could not increase the number of CD11b⁺Gr1⁺ cells in tumor-burdened SCID mice or promote metastases of low metastatic colon cancer cells, the existence of CXCL17-responding myeloid-derived cells caused a striking enhancement of xenograft tumor formation.</p> <h3>Conclusions/Significance</h3><p>These results suggest that aberrant expression of CXCL17 in tumor cells recruits immature myeloid-derived cells and promotes tumor progression through angiogenesis.</p>