ArticleOncotarget2020
Diabetes mellitus is associated with liver metastasis of colorectal cancer through production of biglycan-rich cancer stroma.
Article in Oncotarget, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 18 citations in OpenAlex.
- Hyperglycemia induces an immunosuppressive microenvironment in colorectal cancer liver metastases by recruiting peripheral blood monocytes through the CCL3-CCR1 axis.Journal for immunotherapy of cancer · 2025Article
- GP73-dependent regulation of exosome biogenesis promotes colorectal cancer liver metastasis.Molecular cancer · 2025Article
- Metabolic syndrome in colorectal cancer liver metastasis: metabolic reprogramming and microenvironment crosstalk.Frontiers in immunology · 2025Review
- Biomimetic Proteoglycans for Intervertebral Disc (IVD) Regeneration.Biomimetics (Basel, Switzerland) · 2024Review
- Macrophages and T cells in metabolic disorder-associated cancers.Nature reviews. Cancer · 2024Review
- Diabetes and Cancer: A Twisted Bond.Oncology reviews · 2024Review
- Impacts of pre-existing diabetes mellitus on colorectal cancer in a mice model.Cancer medicine · 2023Article
- Review
- Oxidized high mobility group B-1 enhances metastability of colorectal cancer via modification of mesenchymal stem/stromal cells.Cancer science · 2022Article
- Article
- A Necessary Role for Increased Biglycan Expression during L1-Mediated Colon Cancer Progression.International journal of molecular sciences · 2021Article
- Biglycan: an emerging small leucine-rich proteoglycan (SLRP) marker and its clinicopathological significance.Molecular and cellular biochemistry · 2021Review
- Hyperglycemia Promotes Liver Metastasis of Colorectal Cancer via Upregulation of Integrin αvβ6.Medical science monitor : international medical journal of experimental and clinical research · 2021Article
- Role of Glycated High Mobility Group Box-1 in Gastric Cancer.International journal of molecular sciences · 2021Article
- Tumor-Associated Extracellular Matrix: How to Be a Potential Aide to Anti-tumor Immunotherapy?Frontiers in cell and developmental biology · 2021Review
- Review
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
High morbidity and mortality of cancer, especially colorectal cancer (CRC), in diabetic patients have been reported. In this study, we investigated the relationship between the presence of diabetes mellitus (blood hemoglobin A1C was 6.5% or higher at the time of diagnosis of CRC) and the progression and liver metastasis of CRC. Histopathological findings in the primary lesions, which were preferential to diabetes-complicated CRC (DM-CRC) and the liver metastasis, were also investigated. Of the 473 CRC patients who underwent curative surgical resection, 148 (31%) had diabetes. In DM-CRC cases, the stage was more advanced, with more cases in stage IV or postoperative disease recurrence. Histopathological findings correlated with liver metastasis in DM-CRC, including budding grade, perineural invasion, and myxomatous tumor stroma, and all were highly correlated with the stage. Additionally, myxomatous stroma showed the strongest correlation with liver metastasis in multivariate analysis. Myxomatous stroma in stage III cases correlated with liver recurrence. The myxomatous stroma was abundant in biglycan protein and contained numerous CD90-positive mesenchymal stem cells (MSCs). In human colon cancer cell line HT29, biglycan expression was induced by high sugar concentration, fatty acids, and insulin, and its contact co-culture with MSCs resulted in enhanced stemness and epithelial-mesenchymal transition phenotype. Thus, DM-CRC has higher malignant phenotypes compared to non-DM-CRC, and the involvement of diabetes-induced biglycan may act as a pathogenic factor.
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