Gal-3 in tumor cells and tumor-associated fibroblasts influences multiple pathways. (IMAGE)
Caption
(A) Analysis of the single-cell RNA-sequencing data reveals major cell types in the tumor microenvironment: epithelial cells, myeloid cells, fibroblasts, and T cells. Relationships among each cell cluster, including LGALS3-positive and LGALS3-negative subpopulations. (B) Intercellular communication between LGALS3-positive epithelial cells (LGALS3+ Epi)/LGALS3-negative epithelial cells (LGALS3− Epi) and neighboring cells. The red arrows indicate significant differences between the Epi and TAF groups. (C) Cell–cell crosstalk, which involves ligand–receptor signaling and cytokine secretion/uptake, indicates that the PPIA-BSG pathway is strongly associated with LGALS3+ Epi in combination with TAFs. (D) Relationships between PPIA and LGALS3 in PAAD from the TCGA database. (E) PPIA expression is greater in most solid tumor types than in normal tissues. The red bars represent tumors, and the black bars represent normal tissues. (F) Individuals with low PPIA expression have prolonged overall survival in PAAD. Cutoff: 50%. (G) The radar chart displays the chromatin immunoprecipitation results for inflammatory factors. The blue arrows show the fold changes in the cytokines that are highly expressed in HPSCs/Gal-3 cells compared with the control. (H) Real-time quantitative PCR was used to validate the up-regulation of CCL2 expression at the mRNA level via rGal-3 treatment. (I) ELISA further validated the increase in CCL2 expression at the protein level in Gal-3-producing HPSCs. (J) Analysis of the single-cell RNA-sequencing data revealed a strong focus on the PPIA-BSG pathway in CCL2-positive fibroblasts. Red indicates a large difference between LGALS3+ Epi and LGALS3− Epi. (K) Protein–protein interaction network analysis via the STRING database revealed significant interactions between LGALS3, BSG, PPIA, CCL2, CCR2, PPP3CA, and NFATC2. “∗" indicates statistical significance. Gal-3, galectin-3; TAF, tumor-associated fibroblast; LGALS3, lectin galactoside-binding soluble 3; PPIA, peptidylprolyl isomerase A; BSG, basigin; PAAD, pancreatic adenocarcinoma; HPSCs, human pancreatic stellate cells; CCL2, C–C motif chemokine 2; CCR2, C–C motif chemokine receptor 2; PPP3CA, protein phosphatase 3 catalytic subunit alpha; NFATC2, nuclear factor of activated T cells 2.
Credit
Yaheng Wu, Guo An, Jia Tong, Wenlong Zhang, Zhihua Tian, Bin Dong, Xijuan Liu, Lin Zhao, Chunxian Ye, Jingtao Liu, Wei Zhao, Huachong Ma
Usage Restrictions
Credit must be given to the creator. Only noncommercial uses of the work are permitted. No derivatives or adaptations of the work are permitted.
License
CC BY-NC-ND