Figure 8

Lung cancer cells at invasion fronts express integrin α5β1, interact with stromal fibronectin (FN) fibrils, and become activated. Adenocarcinomas from patients 1 (a,e), 2 (b,c) and 3 (d) were subjected to immunofluorescent (IF) staining and then confocal microscopy. T, cluster of cancer cells. Small arrows point co-localization of two kinds of IF signals at invasion fronts in (a–c), or positive signals for activated cancer cells (d,e). Insets, magnified views of the indicated boxed areas. Scale bars, 10 μm. (a) Integrin (Itg) α5β1 (red), FN (green) and DAPI (blue). (b) Itg α5β1 (red), α-tubulin (green) and DAPI (blue). Yellow arrows indicate cancer cells having singly invaded into stroma. (c) A merged image of FN (red), α-tubulin (green) and DAPI (blue) in a serial section of (b). (d) FN (red), p-Erk (green) and DAPI (blue). (e) FN (red), p-Akt (green) and DAPI (blue). Asterisks indicate inner cancer cells. Note that cancer cells invading deeply into FN-rich stroma (arrows) show stronger positive signals of p-Erk and p-Akt than inner cancer cells (asterisks) in (d,e). (f) A schematic model of cancer cell migration on fibroblast protrusion via integrin α5β1/fibronectin interaction.