Crosstalk between cancer-associated fibroblasts and non-neuroendocrine tumor cells in small cell lung cancer involves in glycolysis and antigen-presenting features

作者：Yuanhua Lu, Hui Li, Peiyan Zhao, Xinyue Wang, Wenjun Shao, Yan Liu, Lin Tian, Rui Zhong, Haifeng Liu, Ying Cheng · 发表于：Molecular Medicine · 年份：2024 · DOI：10.1186/s10020-024-01051-y · 被引用次数：13 · 研究领域：Lung Cancer Research Studies、Cancer, Hypoxia, and Metabolism、Glycosylation and Glycoproteins Research

BACKGROUND: Small cell lung cancer (SCLC) is a highly fatal malignancy, the complex tumor microenvironment (TME) is a critical factor affecting SCLC progression. Cancer-associated fibroblasts (CAFs) are crucial components of TME, yet their role in SCLC and the underlying mechanisms during their interaction with SCLC cells remain to be determined. METHODS: Microenvironmental cell components were estimated using transcriptome data from SCLC tissue available in public databases, analyzed with bioinformatic algorithms. A co-culture system comprising MRC5 fibroblasts and SCLC cell lines was constructed. RNA sequencing (RNA-seq) was performed on co-cultured and separately cultured MRC5 and H196 cells to identify differentially expressed genes (DEGs) and enriched signaling pathways. Glycolysis and STING signaling in SCLC cells were assessed using glucose uptake assays, qRT-PCR, and Western blot analysis. Immunohistochemical staining of SCLC tissue arrays quantified α-SMA, HLA-DRA and CD8 expression. RESULTS: Non-neuroendocrine (non-NE) SCLC-derived CAFs exhibited more abundance and DEGs than NE SCLC-derived CAFs did, which interact with non-NE SCLC cells can induce the enrichment of glycolysis-related genes, increasement of glucose uptake, upregulation of glycolytic signaling proteins in non-NE SCLC cells and accumulation of lactate in the extracellular environment, confirming CAF-mediated glycolysis promotion. Additionally, glycolysis-induced ATP production activated STING signalin...