ArticleJournal of translational medicine2024
Spatial transcriptomics reveals tumor-derived SPP1 induces fibroblast chemotaxis and activation in the hepatocellular carcinoma microenvironment.
Article in Journal of translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed.
- Cancer-associated fibroblasts in therapeutic resistance of hepatocellular carcinoma: evidence, mechanisms, and translational implications.Medical oncology (Northwood, London, England) · 2026Review
- Unraveling the tapestry: Lessons from multi-omics and spatial biology in hepatocellular cancer.Hepatology (Baltimore, Md.) · 2026Review
- YAP1 induces hepatocellular carcinoma via DNA demethylation rather than by canonical driver gene mutations.Communications biology · 2026Article
- Fusion-driven oncogenic programs shape the immune landscape in translocation renal cell carcinoma.Nature communications · 2026Article
- Article
- Molecular phenotypes and spatial archetypes: A new framework for cancer-associated fibroblasts.Cancer cell · 2026Review
- From steatosis to metastasis: microenvironmental reprogramming of the liver in metabolic dysfunction-associated steatotic liver disease.Clinical and molecular hepatology · 2026Review
- Decoding the functional landscape of long non-coding RNAs in hepatocellular carcinoma: molecular mechanisms, clinical implications, and therapeutic prospects.Journal of the Egyptian National Cancer Institute · 2026Review
- Article
- Diet-Microbiota-Immune Interactions in Hepatocellular Carcinoma: An Immunometabolic and Spatial Perspective.Nutrients · 2026Review
- Bidirectional crosstalk between cancer-associated fibroblasts and tumor immunity: shaping the microenvironment and response to immune checkpoint therapy.Experimental hematology & oncology · 2026Review
- Targeted suppression of SPP1 inhibits tumor invasion and metastasis in NRF2 hyperactivated cisplatin resistant HNSCC.Journal of translational medicine · 2026Article
- STK25 inhibits cancer-associated fibroblast activation to overcome cetuximab resistance in colorectal cancer.Clinical and translational medicine · 2026Article
- Immunotherapy in hepatocellular carcinoma: translating mechanistic insights into clinical advances.Clinical and experimental medicine · 2026Review
- CD44 upregulation in chronic liver disease marks the transition to hepatocellular carcinoma and portends poor prognosis.British journal of cancer · 2026Article
- Integrated single-cell and bulk RNA sequencing unravels neutrophil heterogeneity and validates SPP1 as a prognostic biomarker in cervical cancer.BMC cancer · 2026Article
- SPP1+ Macrophages and the Orchestration of Spatially Organized Immunosuppression in Cancer.Biomedicines · 2026Review
- Role of tumor microenvironment in regulator of tumor progression and immunotherapy.Discover oncology · 2026Review
- Macrophage Niche Reconstitution Reveals Dynamic Transcriptional and Communication Networks Renal Macrophage-Epithelial Communication.Research square · 2026Article
- Single-cell transcriptomics and a boundary wound model reveal temporal decoupling and microenvironmental heterogeneity in radiation-induced fibrosis.Frontiers in oncology · 2026Article
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Abstract
backgroundThe tumor microenvironment (TME) exerts profound effects on tumor progression and therapeutic efficacy. In hepatocellular carcinoma (HCC), the TME is enriched with cancer-associated fibroblasts (CAFs), which secrete a plethora of cytokines, chemokines, and growth factors that facilitate tumor cell proliferation and invasion. However, the intricate architecture of the TME in HCC, as well as the mechanisms driving interactions between tumor cells and CAFs, remains largely enigmatic.
methodsWe analyzed 10 spatial transcriptomics and 12 single-cell transcriptomics samples sourced from public databases, complemented by 20 tumor tissue samples from liver cancer patients obtained in a clinical setting.
resultsOur findings reveal that tumor cells exhibiting high levels of SPP1 are preferentially localized adjacent to hepatic stellate cells (HSCs). The SPP1 secreted by these tumor cells interacts with the CD44 receptor on HSCs, thereby activating the PI3K/AKT signaling pathway, which promotes the differentiation of HSCs into CAFs. Notably, blockade of the CD44 receptor effectively abrogates this interaction. Furthermore, in vivo studies demonstrate that silencing SPP1 expression in tumor cells significantly impairs HSC differentiation into CAFs, leading to a reduction in tumor volume and collagen deposition within the tumor stroma.
conclusionsThis study delineates the SPP1-CD44 signaling axis as a pivotal mechanism underpinning the interaction between tumor cells and CAFs. Targeting this pathway holds potential to mitigate liver fibrosis and offers novel therapeutic perspectives for liver cancer management.
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