CXCL17 Expression by Tumor Cells Recruits CD11b(+)Gr1(high)F4/80(-) Cells and Promotes Tumor Progression

Background

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.

Methodology/Principal Findings

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 in vitro, 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 in vitro. 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.

Conclusions/Significance

These results suggest that aberrant expression of CXCL17 in tumor cells recruits immature myeloid-derived cells and promotes tumor progression through angiogenesis.