ArticleOncoTargets and therapy2020
HSPA12B Secreted by Tumor-Associated Endothelial Cells Might Induce M2 Polarization of Macrophages via Activating PI3K/Akt/mTOR Signaling.
Article in OncoTargets and therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 27 citations in OpenAlex.
- Recent insights into HSP70: proteostasis and beyond.Frontiers in molecular biosciences · 2026Review
- The role and significance of the PI3K/Akt-mTOR signaling pathway in infectious diseases.Frontiers in cellular and infection microbiology · 2026Review
- Glioma stem cells: drivers of tumor progression and recurrence.Stem cell research & therapy · 2025Review
- Role of the AKT signaling pathway in regulating tumor-associated macrophage polarization and in the tumor microenvironment: A review.Medicine · 2025Review
- Decoding inflammatory regulation in ovarian cancer at single-cell resolution.Frontiers in immunology · 2025Review
- Microbiome-macrophage crosstalk in the tumor microenvironment: implications for oral squamous cell carcinoma progression and therapy.Frontiers in immunology · 2025Review
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- Cold and hot tumors: from molecular mechanisms to targeted therapy.Signal transduction and targeted therapy · 2024Review
- Detailed role of SR-A1 and SR-E3 in tumor biology, progression, and therapy.Cell biochemistry and biophysics · 2024Review
- A signature based on circadian rhythm-associated genes for the evaluation of prognosis and the tumour microenvironment in HNSCC.Scientific reports · 2024Article
- Stromal cells in the tumor microenvironment: accomplices of tumor progression?Cell death & disease · 2023Review
- Whole genome and RNA sequencing analyses for 254 Taiwanese hepatocellular carcinomas.Biomarker research · 2023Article
- Article
- Polarization Behavior of Bone Macrophage as Well as Associated Osteoimmunity in Glucocorticoid-Induced Osteonecrosis of the Femoral Head.Journal of inflammation research · 2023Review
- The Nocardia Rubra Cell Wall Skeleton Regulates Macrophages and Promotes Wound Healing.Current issues in molecular biology · 2022Article
- Targeting the tumor stroma for cancer therapy.Molecular cancer · 2022Review
- Human Umbilical Cord Mesenchymal Stem Cells Improve the Necrosis and Osteocyte Apoptosis in Glucocorticoid-Induced Osteonecrosis of the Femoral Head Model through Reducing the Macrophage Polarization.International journal of stem cells · 2022Article
- Macrophage scavenger receptors: Tumor support and tumor inhibition.Frontiers in oncology · 2022Review
- Exploring the molecular mechanism of hepatitis virus inducing hepatocellular carcinoma by microarray data and immune infiltrates analysis.Frontiers in immunology · 2022Article
- Comprehensive Pan-Cancer Analysis of Heat Shock Protein 110, 90, 70, and 60 Families.Frontiers in molecular biosciences · 2021Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeThe intratumoral microenvironment of head and neck squamous cell carcinoma (HNSC) is highly immunosuppressive. In this study, we explored the potential functional role of HSPA12B secreted by tumor-associated endothelial cells (TECs) in M2 polarization of macrophages. MATERIALS AND
methodsBulk-seq data from TCGA-HNSC and single-cell RNA-seq data from GSE103322 (with over 5000 cells from 18 primary HNSC cases) were used for bioinformatic analysis. RAW264.7 cell line was used for in vitro studies.
resultsTECs in HNSC had significantly higher expression and secretion of HSPA12B, compared to normal human umbilical vein endothelial cells (HUVECs). Exogenous HSPA12B treatment increased the expression of M2 macrophage marker CD163 and CD206 on RAW264.7 cells in a dose-dependent manner but had no significant influence on CD86, an M1 macrophage marker. OLR1, a known receptor of HSP70 proteins, was specifically expressed in tumor-associated macrophages (TAMs) in HNSC. OLR1 knockdown significantly impaired HSPA12B uptake by RAW264.7 cells and weakened HSPA12B-induced CD163 and CD206 upregulation. HSPA12B treatment increased the expression of p-PI3K, p-Akt and p-mTOR in a dose-dependent manner in RAW264.7 cells. OLR1 inhibition and LY294002 treatment significantly weakened the effects HSPA12B on activating the PI3K/Akt/mTOR signaling and M2 marker expression.
conclusionBased on these findings, we speculated that aberrantly expressed and secreted HSPA12B by TECs could be taken by macrophages partly via OLR1, leading to subsequent activation of the PI3K/Akt/mTOR signaling pathway and elevated expression of M2 markers. This mechanism shows a novel cross-talk between TECs and TAMs, which contributes to the intratumoral immunosuppressive microenvironment.
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