Hypoglycemia links with local invasion/angiogenesis. (A) Representative H&E staining pictures show larger necrotic area in tumors formed by hyperglycemic cells; high glucose (H), hyperglycemic cells; low glucose (L), hypoglycemic cells; scale bar: 100 μm. (B) Representative IHC pictures of cleaved-caspases 3 (left panel) and Caix (right panel) show tumor necrosis in tumors formed by hyperglycemic (H) and hypoglycemic (L) PDAC cells; H, high glucose; L, low glucose. (C) Representative IHC pictures of phospho-histone H3 (pH-H3, left panel) and quantitative analysis (right panel) demonstrate the proliferation status in vivo, scale bar: 100 μm. (D) Representative pictures of CD31 staining (left panel) and microvessel density calculation (right panel) demonstrate increased angiogenesis in tumors formed by hyperglycemic cells, scale bar: 100 μm. (E) Vascular endothelial growth factor type A (Vegfa) enzyme-linked immunosorbent assay shows vascular endothelial growth factor type A secretion in hyperglycemic and hypoglycemic PDAC cells. (F) Heatmap of genes related to angiogenesis indicated on the right; voxel color: transcriptional up-regulation (red) and down-regulation (blue) as compared with the mean. (G) Representative IHC pictures (left panel) and quantitative analysis (right panel) show higher rate of E-cadherin loss in tumors derived from hypoglycemic (L) cells compared with hyperglycemic (H) cells. (H) Invasion (left panel) and migration (right panel) assay demonstrate invasion and migration capacities of hyperglycemic and hypoglycemic PDAC cells in vitro. All data are presented as mean ± standard deviation, and data from 3 independent experiments are shown. Unpaired t test is applied, *P < .05.