Journal: Cancer Research

Article Title: Targeting LRRC15 in Cancer-Associated Fibroblasts Modifies the Extracellular Matrix and Enhances Tumor Immune Responses to Suppress Lung Cancer Progression

doi: 10.1158/0008-5472.CAN-25-2871

Figure Lengend Snippet: LRRC15 promotes M2 polarization by modulating the ECM production. A, Bar plot showing the enriched pathways of the upregulated genes in TGFβ-treated human CAFs compared with those of LRRC15 -KO CAFs, based on bulk RNA-seq data. B, Scatter plot showing the correlation between the ECM organization signature score and LRRC15 expression level in lung cancer from TCGA. Pearson correlation coefficient R is indicated. C, Bar plot showing the enriched pathways in human LRRC15 + CAFs from lung cancer, based on scRNA-seq data. D, Bar plot showing the enriched pathways in mouse LRRC15 + CAFs from TC1-GFP tumor co-injected with TGFβ-treated CAFs, based on scRNA-seq data. E and F, Collagen expression detected using Sirius Red staining in TGFβ-treated mouse ( E ) and human ( F ) WT or LRRC15 -KO CAFs ( n = 3 wells per group). G, Western blot plots showing collagen I expression in WT or LRRC15 -KO human CAFs treated with or without TGFβ for 48 hours. H, Sirius Red staining of tumors from Col1a2- CreER; Lrrc15 fl/fl and littermate Lrrc15 fl/fl mice bearing KPS tumors ( n = 3–4 mice per group). I, Cell number and proportion of CD206 + BMDMs in mouse BMDM and CAF ECM coculture assay ( n = 3 wells per group). J, Cell number and proportion of CD206 + mo-MΦs in human mo-MΦs and CAF ECM coculture assay ( n = 3 wells per group). K, Proportion and cell number of CD206 + mo-MΦs of CD206 in human mo-MΦs cultured with or without recombinant human collagen I ( n = 3 wells per group). Data are presented as mean ± SEM, Statistical significance was determined using the hypergeometric test ( A , C , and D ) or unpaired two-tailed Student t test ( E , F , H , I , J , and K ). P values were adjusted using the Benjamini–Hochberg method ( A , C , and D ).

Article Snippet: For macrophage–collagen stimulation assays, 500 μg/mL human collagen I (MedChemExpress, cat. #HY-NP160) was coated in 12-well plates for culturing mo-MΦs.

Techniques: RNA Sequencing, Expressing, Injection, Staining, Western Blot, Co-culture Assay, Cell Culture, Recombinant, Two Tailed Test