Fig. 4: Injury-induced stromal remodeling in lobular invasion.

a Fractions of tumor in proximity (within 20 µm) with other cell- and tissue classes by distance to the lobular invasion front. Right panel: magnification of the first 50 µm from the invasion front. n = 5 tumors, n = 15 regions of interest (ROIs). b Example of immunohistochemistry (IHC) of nerve growth factor receptor (NGFR; red) co-labelled with cluster of differentiation (CD)146 (brown). Representative of n = 4 tumors. c Schematic of the murine acute pancreatitis model⁴⁰. Mice were injected with either caerulein (n = 2) or saline (n = 2; control). Three days after the injection, pancreata were retrieved and single-cell RNA sequencing (scRNA-seq) performed. d NGFR signature of mice with induced pancreatitis (n = 2) or saline-injected control mice (n = 2). e Proportional Venn diagram of overlapping marker expression with the NGFR⁺ population from the murine acute pancreatitis model. Data from n = 124 NGFR⁺ cells from n = 4 mice. f Mean NGFR intensity (IHC quantifications of human tumors) within a 50 µm radius area expanded from tumor cells (n = 5103 cells) in regions of lobular invasion by distance to the lobular invasion front. Orange line: rolling average of NGFR intensity near each individual tumor cell and standard deviation (blue). Pink and cyan dashed lines: averages of NGFR intensity of the expanded area from acinar cells (n = 5702) and acinar cells undergoing acinar-to-ductal metaplasia (ADM, n = 10430), respectively (n = 4 tumors, n = 12 ROIs). g NGFR⁺ area of pancreatic lobules with different degrees of atrophy and tumor invasion (n = 67 ROIs). Data from n = 8 individual tumors. Unpaired two-tailed Kruskal–Wallis rank sum test, with Benjamini–Hochberg (BH)-corrected post-hoc Dunn’s test for pairwise multiple comparisons. BH-corrected p-values are given. Box-and-Whisker plots show the median (line), the interquartile range (IQR, box), and minimum and maximum values within 1.5 times IQR from the first and third quartile (whiskers). Source data are provided in the Source Data file.