Fig. 1: Definition of coadaptation stages.

a Recognition of the coadaptation process between disseminated tumour cells (DTCs) and hepatocytes in liver metastasis of PDAC. b Brief procedure displaying the intrasplenic injection model for the liver metastasis process study. (c) Liver metastasis model by intrasplenic injection of murine Kpc1199luc cells followed by CT combined with 3D organ reconstruction bioluminescence imaging to assess the time point. Mice that received an intrasplenic injection were photographed to detect the normal liver (NL), (Day 3, D3), premetastatic niche (PMN), (Day 8, D8) and macrometastatic niche (MMN) (Day 15, MMN). Red, reconstructed liver; orange, reconstructed spleen; yellow, signals of tumour niches. Reconstructed organ opacity, left, 100%; right, 20%. Scale colour bar: 2.00 × 105−2.00 × 107 (n = 5 mice per group). d Representative livers from liver metastasis mouse models showing an NL (D3), PMN (D8) or MMN (D15) after injection (n = 5 mice per group). e IHC-P staining of GFP in left lobules from mouse models showing an NL (D3), PMN (D8) or MMN (D15) (n = 5 samples per group, 3 fields assessed per sample). Scale bars, 100 μm. f Representative IHC-P staining of the PMN-specific secreted protein markers LOX, SAA1/2, MIF or TIMP1 in the left lobules of livers from model mice to detect an NL (D3), PMN (D8) or MMN (D15) (n = 5 samples per group, 3 fields assessed per sample). Scale bars, 100 μm; * represents metastatic niches. g, h Representative IHC-P staining of PMNs expressing the tumour-associated macrophage (TAM) markers CD68, CD11b, CD163 and Ly-6G in the left lobules of livers from mouse models to detect an NL (D3), PMN (D8) or MMN (D15) (n = 5 samples per group, 3 fields assessed per sample). Scale bars, 100 μm; * represents metastatic niches. (n = 5 samples per group, mean ± SEM, two-tailed unpaired t test, 3 fields assessed per sample). i Representative IHC-P staining of the PMN-specific secreted protein marker LOX and TAM markers CD68 and CD163 in the left lobules of livers from model mice on D8 bearing sham, LTPA modelling and Kpc1199 modelling (n = 5 samples per group, 3 fields assessed per sample). Scale bars, 100 μm. Source data are provided in the Source Data file.