CXCL8/SDC1 axis mediates tumor stem cell interactions to drive remote transfer in thyroid cancer

This study explores the molecular mechanisms behind the remote transfer of thyroid cancer (THCA) by investigating the interaction network of C-X-C motif chemokine ligand 8⁺ (CXCL8⁺ monocytes and syndecan-1⁺ (SDC1⁺) tumor stem cells using single-cell and spatial transcriptome sequencing. Tumor samples from THCA patients were analyzed using single-cell RNA sequencing (scRNA-seq), spatial transcriptome sequencing, and tumor tissue transcriptome analysis. Data were processed with Seurat and CellChat R packages, integrated via the SPOTlight package, and correlated with clinical data from the UCSC Xena database. Functional pathway enrichment analyses were performed using Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genome (KEGG). In vitro, a co-culture system of monocytes and THCA stem cells was developed, and protein levels were measured via enzyme-linked immunosorbent assay (ELISA) and Western blotting. The self-renewal and migration of follicular thyroid carcinoma (FTC) 238-S cells were assessed through sphere formation, colony formation, Cell Counting Kit-8 (CCK-8), and Transwell assays. In vivo, a subcutaneous tumor xenograft model and a lung metastasis model were established in nude mice. Transcriptomic analyses identified the CXCL8/SDC1 axis as a key mediator of Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling activation, promoting THCA stem cell self-renewal, invasion, and metastasis. CXCL8/SDC1 expression was significantly higher in the high-risk C1 subtype of THCA patients and correlated with a worse prognosis. In vitro and animal studies confirmed that the CXCL8/SDC1 axis drives tumor progression and metastasis. The interaction between CXCL8⁺ monocytes and SDC1⁺ tumor stem cells activates the JAK-STAT pathway, facilitating the remote transfer of THCA. Targeting the CXCL8/SDC1 axis may provide novel therapeutic strategies for improving THCA patient outcomes.