{"doi":"10.1016/j.celrep.2025.116342","title":"Neuropeptide adrenomedullin remodels stemness and macrophage dynamics in glioblastoma","abstract":"The presence of self-renewing glioblastoma (GBM) stem cells (GSCs) and infiltrating pro-tumor macrophages constitutes two key hallmarks of GBM. Here, we identified the neuropeptide adrenomedullin (ADM) as a key factor regulating GSC-macrophage symbiosis. Epidermal growth factor receptor (EGFR) overexpression upregulates ADM in GSCs to enhance their self-renewal, glycolysis, and tumor growth by activating the signal transducer and activator of transcription 3 (STAT3) pathway. GSC-secreted ADM promotes macrophage infiltration and pro-tumor reprogramming through activation of ADM receptor (ADMR), thereby engaging both STAT3 and STAT6 pathways. In GBM mouse and patient-derived xenograft (PDX) models, inhibition of the ADM-ADMR axis, STAT3, or STAT6 suppresses tumor progression, GSC self-renewal, and pro-tumor macrophage abundance, with dual inhibition of STAT3 and STAT6 leading to durable complete tumor regression in a subset of tumor-bearing mice. In human GBM tumors and plasmas, ADM correlates positively with GSC stemness, pro-tumor macrophage abundance, and poor prognosis. These findings highlight ADM-triggered GSC-macrophage symbiosis as a promising therapeutic target for GBM.","journal":"Cell Reports","year":2025,"id":547151,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9545,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":584749,"name":"Fatima Khan","orcid":"0000-0002-8860-0339","position":1,"is_corresponding":false},{"id":628136,"name":"Wenjing Xuan","orcid":"0000-0002-0535-2828","position":2,"is_corresponding":false},{"id":105301,"name":"Yang Liu","orcid":"0000-0002-5221-7725","position":3,"is_corresponding":false},{"id":1439582,"name":"Yuyun Huang","orcid":null,"position":4,"is_corresponding":false},{"id":1439583,"name":"Donovan Whitfield","orcid":null,"position":5,"is_corresponding":false},{"id":420818,"name":"Lizhi Pang","orcid":"0000-0002-7331-7514","position":6,"is_corresponding":false},{"id":243053,"name":"Peiwen Chen","orcid":"0000-0002-8129-9328","position":7,"is_corresponding":false},{"id":792808,"name":"Heba Ali","orcid":"0000-0001-5535-7638","position":0,"is_corresponding":true}],"reference_count":69,"raw_metadata":null,"created_at":"2026-07-19T02:53:36.567932Z","pmid":"41004340","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}