ArticleJournal of experimental & clinical cancer research : CR2021
Tumor cell-derived SPON2 promotes M2-polarized tumor-associated macrophage infiltration and cancer progression by activating PYK2 in CRC.
Article in Journal of experimental & clinical cancer research : CR, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 106 citations in OpenAlex.
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- Remodeling the Immune Landscape: How Obesity-Induced SASPs Create a Pro-Tumorigenic Niche.Current obesity reports · 2026Review
- Identification and functional validation of SPON2 as a novel biomarker for the diagnosis and prognosis in hepatocellular carcinoma.Journal of gastrointestinal oncology · 2026Article
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- Cytokines and Chemokines as Emerging Biomarkers and Therapeutic Targets in Colorectal Cancer-Narrative Review.International journal of molecular sciences · 2026Review
- HERV6196 as an enhancer with oncogenic potential in rectal cancer.Microbiology spectrum · 2026Article
- Integrative Multiomics Analysis Reveals Tumor-Associated Macrophage Heterogeneity and a Prognostic Signature in Gastric Cancer.Human mutation · 2026Article
- Biomechanical signaling of cytoskeleton and membrane reorganization in tumor immune chemotactic migration.Theranostics · 2026Review
- Macrophages in Colorectal Cancer: from Normal Mucosa to Distant Metastasis: Beyond the M1/M2 Paradigm.Journal of Cancer · 2026Review
- Rewiring tumor-associated macrophages in hepatocellular carcinoma.Frontiers in immunology · 2026Review
- Calycosin ameliorates inflammation and M1 macrophage polarization via Spon2 in LPS-triggered MH-S alveolar macrophages.Journal of natural medicines · 2025Article
- Liver metastasis of colorectal cancer: Mechanism and clinical therapy (Review).Oncology reports · 2025Review
- Predictive value of inflammatory marker PLR in prostate cancer.BMC urology · 2025Article
- SPON2 facilitates osteosarcoma development by inducing M2 macrophage polarization through activation of the NF-κB/VEGF signaling axis.Cell death discovery · 2025Article
15 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTumor-associated macrophages (TAMs) are key regulators of the complex interplay between cancer and the immune microenvironment. Tumor cell-derived spondin 2 (SPON2) is an extracellular matrix glycoprotein that has complicated roles in recruitment of macrophages and neutrophils during inflammation. Overexpression of SPON2 has been shown to promote tumor cell migration in colorectal cancer (CRC). However, the mechanism by which SPON2 regulates the accumulation of TAMs in the tumor microenvironment (TME) of CRC is unknown.
methodsImmunohistochemistry was used to examine SPON2 expression in clinical CRC tissues. In vitro migration assays, transendothelial migration assays (iTEM), and cell adhesion assays were used to investigate the effects of SPON2 on monocyte/macrophage migration. Subcutaneous tumor formation and orthotopic implantation assays were performed in C57 BL/6 mice to confirm the effects of SPON2 on TAM infiltration in tumors.
resultsSPON2 expression is positively correlated with M2-TAM infiltration in clinical CRC tumors and poor prognosis of CRC patients. In addition, SPON2 promotes cytoskeletal remodeling and transendothelial migration of monocytes by activating integrin β1/PYK2 axis. SPON2 may indirectly induce M2-polarization through upregulating cytokines including IL10, CCL2 and CSF1 expression in tumor cells. Blocking M2 polarization and Macrophage depletion inhibited the SPON2-induced tumors growth and invasion. Furthermore, blocking the SPON2/integrin β1/PYK2 axis impairs the transendothelial migration of monocytes and cancer-promoting functions of TAMs in vivo.
conclusionsOur findings demonstrate that SPON2-driven M2-TAM infiltration plays an important role during CRC tumor growth and metastasis. SPON2 may be a valuable biomarker guiding the use of macrophage-targeting strategies and a potential therapeutic target in advanced CRC.
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