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Journal: Cancer Research
Article Title: Cancer-Associated Fibroblasts Foster a High-Lactate Microenvironment to Drive Perineural Invasion in Pancreatic Cancer
doi: 10.1158/0008-5472.CAN-24-3173
Figure Lengend Snippet: pCAFs enhance PNI of pancreatic cancer via lactate-mediated H3K18la in vivo . A, Gross and surgical images, hematoxylin and eosin (H&E) staining, and mIF images. mIF showed pan-lac, H3K18, L1CAM, and SLIT1 expression in the sciatic nerve invasion model. The dotted line indicates the tumor boundary. Tuj1 served as a neuronal marker, and CK19 was used as a tumor marker. H&E, scale bars, 1,000 μm. mIF, scale bars, 200 μm. B, Sciatic nerve function scores and sciatic nerve indexes of mice treated as indicated ( n = 5 mice per group). Kruskal–Wallis test with Dunn multiple comparisons test; data are shown as the means ± SD. C–E, KPC mice (LSL- KRAS G12D/ + ; LSL- TRP53 R172H / + ; PDX- 1- CRE +/+ ) were divided into four groups, with three groups respectively receiving i.p. injections of sodium lactate (1 g/kg), oral administration of the MCT1 inhibitor AZD3965 (100 mg/kg), and i.p. injections of heptenoic acid (1 mg/kg). n = 10 mice per group. C, Representative hematoxylin and eosin staining. mIF and 3D reconstruction images showing PNI status and pan-lac, H3K18, L1CAM, and SLIT1 expression in KPC mice treated as indicated. Tuj1 served as a neuron marker. CK19 was used as a tumor marker. Hematoxylin and eosin and mIF, scale bars, 200 μm. 3D scale bars, 500 μm. D, Proportion of PNI in KPC mice under the specified treatments ( n = 10 mice per group). Fisher exact test. E, Nerve density percentage (left) and number (right) in KPC mice following the indicated treatments ( n = 10 mice per group; χ 2 test). *, P < 0.05. HA, heptenoic acid.
Article Snippet:
Techniques: In Vivo, Staining, Expressing, Marker