Fig. 2. Tumor cell-derived G-CSF is pro-metastatic or anti-metastatic depending on the host NK cell presence.
a, b Neutrophilia caused by G-csf-overexpression in tumor cells increased metastatic colonization in NOD-scid mice, but not in NSG mice in a modified experimental metastasis model. Following the experimental design as in a, the metastatic progression of E0771-Luc cells was monitored by BLI. Quantification of photon flux and comparison of metastatic colonization in the lungs of mice are shown (b). n = 9 mice per group. P value was determined by two-way ANOVA. c–g As depicted in c, NSG mice (d, e), and NOD-scid mice (f, g) were orthotopically implanted with E0771-Luc or E0771-Luc-g-csf cells. At the endpoint (day 30 for NOD-scid and day 20 for NSG mice), the spontaneous lung metastases were assessed by ex vivo BLI (d, f), and the primary tumors were also dissected and weighed (e, g). n = 10 (d, e) or 8 (f, g) mice per group. P values were determined by unpaired two-tailed t-test. ns, not significant. h, i Neutrophil depletion abolished the metastasis-regulating effects of tumor cell G-csf overexpression in the experimental metastasis model. A schematic diagram was depicted in h showing the experimental design. Quantification of photon flux and comparison of metastatic colonization in the mouse lungs are shown on the top, and the endpoint bioluminescence images of lungs are shown on the bottom (i). n = 5 mice per group. P values were determined by two-way ANOVA. ns not significant. Ly6Gab: Anti-Ly6G antibody. j In the 4T1 spontaneous metastasis model neutrophil depletion showed anti-metastatic and pro-metastatic effects in NK-cell competent (BALB/c and NOD-scid) and NK cell-deficient (NSG) mice, respectively. The lung metastases were examined by ex vivo BLI and quantification of photon flux of lungs are shown. n = 9 (IgG group) and 8 (Ly6Gab group) for BALB/c mice; and n = 5 per group for NOD-scid and NSG mice. P values were determined by unpaired two-tailed t-test. Data are represented as mean ± SEM. Source data are provided as a Source data file.