{"doi":"10.3390/ijms232314613","title":"Microglia-Derived Olfactomedin-like 3 Is a Potent Angiogenic Factor in Primary Mouse Brain Endothelial Cells: A Novel Target for Glioblastoma","abstract":"Neoangiogenesis, a hallmark feature of all malignancies, is robust in glioblastoma (GBM). Vascular endothelial growth factor (VEGF) has long been regarded as the primary pro-angiogenic molecule in GBM. However, anti-VEGF therapies have had little clinical efficacy, highlighting the need to explore VEGF-independent mechanisms of neoangiogenesis. Olfactomedin-like 3 (OLFML3), a secreted glycoprotein, is an established proangiogenic factor in many cancers, but its role in GBM neoangiogenesis is unknown. To gain insight into the role of OLFML3 in microglia-mediated angiogenesis, we assessed endothelial cell (EC) viability, migration and differentiation following (1) siRNA knockdown targeting endogenous EC Olfml3 and (2) EC exposure to human recombinant OLFML3 (rhOLFML3; 10 ng/mL, 48 h), and conditioned medium (CM) from isogenic control and Olfml3−/− microglia (48 h). Despite a 70% reduction in Olfml3 mRNA levels, EC angiogenic parameters were not affected. However, exposure to both rhOLFML3 and isogenic control microglial CM increased EC viability (p < 0.01), migration (p < 0.05) and differentiation (p < 0.05). Strikingly, these increases were abolished, or markedly attenuated, following exposure to Olfml3−/− microglial CM despite corresponding increased microglial secretion of VEGF-A (p < 0.0001). Consistent with reports in non-CNS malignancies, we have demonstrated that OLFML3, specifically microglia-derived OLFML3, promotes VEGF-independent angiogenesis in primary brain microvascular ECs and may provide a complementary target to mitigate neovascularization in GBM.","journal":"International Journal of Molecular Sciences","year":2022,"id":268162,"datarank":0.29188652235829704,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.0,"self_endowment_contribution":0.29188652235829704,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9624,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":730923,"name":"Ryan G. Toedebusch","orcid":null,"position":1,"is_corresponding":false},{"id":730924,"name":"Eshetu Debebe","orcid":null,"position":2,"is_corresponding":false},{"id":930356,"name":"Aurelie H. Bastian","orcid":null,"position":3,"is_corresponding":false},{"id":730398,"name":"Christopher A. Lucchesi","orcid":"0000-0001-8767-7003","position":4,"is_corresponding":false},{"id":930357,"name":"Shafee Syed-Quadri","orcid":null,"position":5,"is_corresponding":false},{"id":730399,"name":"Luke A. Wittenburg","orcid":"0000-0002-5543-0724","position":6,"is_corresponding":false},{"id":341962,"name":"Xinbin Chen","orcid":"0000-0002-4582-6506","position":7,"is_corresponding":false},{"id":793287,"name":"Frederick J. Meyers","orcid":"0000-0002-4456-4647","position":8,"is_corresponding":false},{"id":730400,"name":"Christine M. Toedebusch","orcid":"0000-0002-3216-3344","position":9,"is_corresponding":false},{"id":930355,"name":"Laila M. Joseph","orcid":null,"position":0,"is_corresponding":true}],"reference_count":38,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:27:10.233250Z","pmid":"36498941","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":[]}