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Archive > Volume 30 Issue 4 > 2023,30(4):302-308. DOI:10.3872/j.issn.1007-385X.2023.04.004 Prev Next
Basic Research
Functional study on galactose-specific lectin 3 from tumor-associated macrophage based on single-cell sequencing
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Abstract:
Objective: To find functional molecules that regulate tumor immune microenvironment (TIME) and influence therapeutic effect and prognosis by focusing on phenotype changes of tumor-associated macrophages (TAM) before and after chemotherapy.Methods: The data set PRJEB45598 from ENA (European Nucleotide Archive) was used to analyze the single-cell sequencing data of biopsy tumor tissues from patients with advanced gastric cancer before and after chemotherapy. 31 subpopulations of cells were obtained using PCA (principal component analysis) and UMAP (uniform manifold approximation and projection). Further TAM subtype analysis and differential gene screening were performed to find the genes highly expressed in M2-like TAM cells after chemotherapy. The mRNA and protein expression changes of the specific gene before and after chemotherapy were verified by subcutaneous melanoma B16-F10 cell transplanted xenograft model. Whether the protein regulates chemotherapy-induced tumor cell death was analyzed in vitro by Incucyte. Results: Focusing on the characteristic expression genes in M2-like TAM in single-cell sequencing data, we found that the mRNA level of galactose-specific lectin 3 (LGALS3) was significantly increased after chemotherapy (P<0.01), and its high expression in various tumors was negatively related to the survival of patients (P<0.05 or P<0.01). LGALS3 washighly expressed in M2-like TAM in melanoma B16-F10 cell transplanted xenograft model in vivo (P<0.01), and its expression was further increased after oxaliplatin chemotherapy (P<0.05). Recombinant LGALS3 protein inhibited oxaliplatin-induced tumor cell deathin vitro. Conclusion: M2-like TAM promotes chemoresistance of tumor cells through synthesis and secretion of LGALS3 after chemotherapy. Therefore, targeting LGALS3 through immunotherapy may effectively improve the therapeutic effect of tumors.
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