CCR7 Regulates B16 murine melanoma cell tumorigenesis in skin

Abstract: Tumor cell-associated chemokine recep-tors play distinct roles in cancer biology, including enhancement of lymph node (LN) metastasis. To de-termine if CCR7 influences tumor formation in skin, we inoculated B16 cells transduced with CCR7 and luciferase (CCR7-luc-B16) or with retroviral vector and luciferase (pLNCX2-luc-B16) into ear skin and footpads of wild-type (WT) mice. In contrast to pLNCX2-luc-B16 cells, 97 % of CCR7-luc-B16 cell-inoculated mice formed skin tumors as well as cervi-cal LN metastases by Day 21 following ear inocula-tion. CCR7-expressing and control B16 cells, how-ever, formed tumors of similar size and with high-efficiency in SCID-beige mice. Cells from both lines accumulated in the skin of WT mice in similar num-bers until Day 7. By Day 11, however, control cells decreased tenfold, whereas CCR7-luc-B16 cells formed small tumor nodules. Tumor cells were infre-quently detected in draining cervical LNs up to 11 days after injection of both cell lines, but stable no-dal metastases were only observed after CCR7-luc-B16 ear tumors had been established (Day 21). ELISPOT assays revealed that IFN--producing cells in draining LNs from CCR7-luc-B16-injected ears were reduced through Day 7. After footpad injec-tion, tumor formation by CCR7-expressing B16 cells was enhanced only with small, initial tumor cell inoc-ula. With larger inocula, tumor formation was equiv-alent, but the numbers of tumor-infiltrating leuko-cytes were reduced by approximately sixfold in CCR7-B16 tumors compared with pLNCX2-B16 tu-mors of equal size. IFN- and CXCL10 were reduced 35- and sixfold, respectively, in CCR7-B16 cell tu-mors (vs. control tumors). Thus, CCR7 expression enhances tumorigenesis in addition to facilitating LN metastasis. J. Leukoc. Biol. 84: 000–000; 2008