Journal: Pharmaceuticals
Article Title: LAMP1 as a Target for PET Imaging in Adenocarcinoma Xenograft Models
doi: 10.3390/ph18081122
Figure Lengend Snippet: Integrated analysis of single-cell RNA sequencing and spatial transcriptomics reveals elevated LAMP1 expression in MDSCs and CAFs with enrichment in tumor regions compared to adjacent normal tissue. ( A ) K-means clustering analysis of single-cell RNA sequencing data highlights distinct cellular populations within the tumor microenvironment. Normalized log2 expression levels of CD68 ( B ), LAMP1 ( C ), CD74 ( D ), and FXYD3 ( E ) across all identified cell populations. ( F ) Quantitative analysis shows high expression of LAMP1 in cancer cells as well as macrophages and CAFs, which are prominent components of the tumor microenvironment. ( G ) Subtype clustering of macrophages identifies functional subsets, allowing for finer delineation of LAMP1 expression within specific macrophage populations. ( H ) Normalized log2 expression of LAMP1 within macrophage subtypes highlights differential expression patterns. ( I ) LAMP1 expression was significantly elevated in the MDSC subtype of macrophages. ( J ) Combined analysis of tumor marker expression within the spatial transcriptomics dataset reveals high expression of FXYD3, human epidermal growth factor receptor 2 (HER2), estrogen receptor (ER), MKI67, topoisomerase II alpha (TOP2A), and epithelial cell adhesion molecule (EPCAM). ( K ) Annotation of cancer cell regions in breast cancer tissue highlights tumor-specific regions. Spatial expression maps show CD74 ( L ), CD68 ( M ), and LAMP1 ( N ) in breast cancer tissue, with notable localization in cancer cells and tumor-associated immune cells. ( O ) Spatial co-expression analysis of CD74, CD68, and LAMP1 with a magnified view and ( P ) comparative analysis of LAMP1 expression between cancerous regions and adjacent normal tissue confirms a significant elevation of LAMP1 in tumor regions. ***: p < 0.001.
Article Snippet: Rabbit anti-human LAMP1 mAb (Novus Biological, Centennial, CO, USA, Cat# NBP2-89844, RRID# AB_3442448) was conjugated to p-SCN-Bn-deferoxamine (DFO) chelator (Macrocyclics, Plano, TX, USA, CAT# B-705) before radiolabeling with 89 Zr according to the standard methods [ ].
Techniques: RNA Sequencing, Expressing, Functional Assay, Quantitative Proteomics, Marker