ICAM2 loss drives 5-fluorouracil resistance via TGF-β/Smad/SP1/PTN-dependent apoptosis evasion and macrophage remodeling in gastric cancer

Figure 7 Intercellular adhesion molecule 2 downregulation promotes M2 macrophage polarization potentially involving pleiotrophin, driving 5-fluorouracil resistance in gastric cancer. A: Representative immunohistochemistry images showing intercellular adhesion molecule 2 (ICAM2) and CD206 expression in chemo-resistant and chemo-sensitive advanced gastric cancer (AGC) tissues. M2 macrophage infiltration was significantly higher in chemo-resistant tissues; B: Correlation analyses between M2 macrophages infiltration and ICAM2 expression in AGC patient specimens; C: Overview of the differentiation protocol used to induce THP-1 cells into M0 macrophages; D: Real-time PCR (RT-PCR) analysis of M1-related (CD80, CD86, TNF-α, CXCL9, iNOS, IL-6) and M2-related (CD163, CD206, IL-10, Arg-1, TGF-β) gene expression in macrophages; E: Western blotting analysis of M1 (CD80, CD86) and M2 (Arg1, CD163, CD206) protein levels in macrophages; F and G: RT-PCR and Western blotting analyses evaluating the potential role of pleiotrophin (PTN) in influencing ICAM2-mediated macrophage polarization; H: Schematic of the transwell system used to investigate the impact of macrophage polarization on GC cell chemoresistance; I-K: Cytotoxicity assays, flow cytometry, and analysis of apoptosis-related proteins assessing the potential involvement of PTN in modulating the effects of ICAM2-induced M2 macrophage polarization on 5-fluorouracil resistance in GC cells. ^aP < 0.05; ^bP < 0.01; ^cP < 0.001; ^dP < 0.0001. ICAM2: Intercellular adhesion molecule 2; PTN: Pleiotrophin; 5-FU: 5-fluorouracil; IC₅₀: Half-maximal inhibitory concentration.