2026-10-13T20:41:54Z https://api.figshare.com/v2/oai

oai:figshare.com:article/33667679 2026-09-12T12:24:05Z category_7 category_12 category_14 category_19 category_734 category_61 category_64 category_133 portal_87 item_type_3 month_year_09_2026

Single-Cell Transcriptomics Uncovers β-Elemene-Induced Macrophage Reprogramming as a Mechanism to Suppress Osteosarcoma Stemness via the CCL2-Akt Axis Shaochun Zhang (5793005) Ting Liu (45625) Jing Ke (2111455) Medicine Cell Biology Molecular Biology Pharmacology Biological Sciences not elsewhere classified Developmental Biology Cancer Plant Biology β-elemene osteosarcoma tumor-associated macrophage cysteine-cysteine Motif Chemokine Ligand 2 protein kinase B pathway <p>β-elemene (ELE), a natural sesquiterpene with antitumor properties, exerts immunomodulatory effects on osteosarcoma (OS), but its impact on the tumor microenvironment and cancer stemness remains unclear. This study investigated how ELE reprograms tumor-associated macrophages (TAMs) to suppress OS progression.</p> <p>We combined single-cell RNA sequencing (scRNA-seq) of a murine OS model with functional validations, including macrophage polarization assays, co-culture systems, western blot, RT-PCR, ELISA, tumorsphere formation, and rescue experiments (CCL2 overexpression, Akt activation).</p> <p>ELE treatment significantly inhibited OS tumor growth and promoted apoptosis. scRNA-seq revealed that ELE skewed TAMs from immunosuppressive M2 to antitumor M1 phenotypes, concurrently reducing the osteosarcoma stem-like cell (OSC) population. Cell communication analysis showed enhanced M1-OSC pro-inflammatory signaling (e.g. TNF, IL-1) and suppressed M2-derived CCL2 signaling. Mechanistically, ELE downregulated CCL2 secretion from M2 macrophages, inhibiting Akt phosphorylation and subsequent β-catenin activation, which led to reduced expression of stemness markers (SOX2, NANOG, CD133) and impaired OSC self-renewal and invasion. These effects were reversed by CCL2 overexpression or Akt activation.</p> <p>ELE attenuates OS stemness by polarizing TAMs toward an M1 phenotype and disrupting the CCL2/Akt/β-catenin axis, revealing a novel immunometabolic mechanism for OS therapy.</p> 2026-09-12T12:24:05Z Dataset Dataset 10.6084/m9.figshare.33667679.v1 https://figshare.com/articles/dataset/Single-Cell_Transcriptomics_Uncovers_-Elemene-Induced_Macrophage_Reprogramming_as_a_Mechanism_to_Suppress_Osteosarcoma_Stemness_via_the_CCL2-Akt_Axis/33667679 CC BY 4.0