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. 2024 Feb 7;626(8000):864–873. doi: 10.1038/s41586-023-06950-4

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© The Author(s) 2024

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — a–e, Bioluminescence analysis of the tumour burden in the liver, lungs, spleen and pancreas of the indicated mice 8 weeks after orthotopic pancreas injection of 2 × 10⁵ KPC-2-luciferase (KPC-2-luci) cells: Flt3^creCsf1r^f/f mice (n = 12) and control Csf1r^f/f littermates (n = 12) (a); Ccr2^−/− mice (n = 12) and Ccr2^+/− littermates (n = 11) (b); Clec4f^creCsf1r^f/f mice (n = 19) and Csf1r^f/f littermates (n = 25) (c); and Clec4f^creSpi1^f/f mice (n = 12) and Spi1^f/f littermates (n = 13) (d). Clec4f^creR26^LSL-DTR mice (n = 26) and R26^LSL-DTR littermates (n = 33) (e) received weekly intraperitoneal injection of DT (Methods) from week 1 to 7. The circles represent individual mice, boxes represent the 25–75% confidence intervals and the whiskers indicate the extreme values. The blue lines indicate the median. The green histograms represent the background bioluminescence imaging signal from wild-type C57BL/6J mice that did not receive tumours (n = 3 mice per group). Results are from at least three independent experiments per genotype. Statistical analysis was performed using two-tailed Mann–Whitney U-tests; P < 0.05 was considered to be significant. f, Schematic of pancreas venous drainage. Pulm., pulmonary. g, Clec4f^creR26^LSL-DTR mice (n = 5) and R26^LSL-DTR littermates (n = 6) received intraportal injection of 3 × 10⁵ KPC-2-luci cells (day 0 (D0)) and DT injections (D−1, D7 and D14). Survival was analysed using log-rank (Mantel–Cox) tests. p.v., portal vein. h, Clec4f^creR26^LSL-DTR (n = 7) and R26^LSL-DTR control (n = 4) mice received DT injection 24 h before intraportal injection of 1 × 10⁶ KPC-1-luci-GFP cells. The numbers of CD45⁻GFP⁺ tumour cells per g of liver were analysed 24 h later using flow cytometry. i, Clec4f^creR26^LSL-DTR mice (n = 7) and R26^LSL-DTR littermates (n = 8) received 1 × 10⁶ KPC-1-luci cells (D0) and DT injections (D−1 and D7), and the livers were analysed at D14 by bioluminescence imaging. Representative liver micrographs are shown on the right. j, Bioluminescence imaging analysis as described in i, with DT injections at D3 and D10 (n = 8 and 6). The circles represent individual mice. Data are mean ± s.d. Statistical analysis was performed using two-tailed unpaired t-tests; P < 0.05 was considered to be significant. For i and j, scale bars, 1 cm.

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