ArticleJournal of translational medicine2010
The tumor microenvironment of colorectal cancer: stromal TLR-4 expression as a potential prognostic marker.
Article in Journal of translational medicine, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 1 of them a synthesis that pooled it.
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Who cites it
83 citing papers in PubMed, 1 synthesis or guideline pooled it, 146 citations in OpenAlex.
- Contribution of TLR4 to colorectal tumor microenvironment, etiology and prognosis.Journal of cancer research and clinical oncology · 2023Pooled it
- Comparative Tumor Microenvironment Analysis for HCC and PDAC Using KMplotter.International journal of molecular sciences · 2025Article
- Baicalein modulates colorectal tumor microenvironment to suppress growth, metastasis, and immune escape.Molecular biology reports · 2025Review
- Hyperglycemia and Obesity as the Key Drivers of Increased Colorectal Cancer Mortality in the North Africa and Middle East Region.Oman medical journal · 2025Article
- Sparstolonin B Suppresses Proliferation and Modulates Toll-like Receptor Signaling and Inflammatory Pathways in Human Colorectal Cancer Cells.Pharmaceuticals (Basel, Switzerland) · 2025Article
- NF-κB pathway and angiogenesis: insights into colorectal cancer development and therapeutic targets.European journal of medical research · 2024Review
- Genetic association and functional implications of TLR4 rs1927914 polymorphism on colon cancer risk.BMC cancer · 2024Article
- The Role of Natural Products from Herbal Medicine in TLR4 Signaling for Colorectal Cancer Treatment.Molecules (Basel, Switzerland) · 2024Review
- A model based on immunogenic cell death-related genes predicts prognosis and response to immunotherapy in kidney renal clear cell carcinoma.Translational cancer research · 2024Article
- Oral Targeted Delivery of Codonopsis Radix Polysaccharide via Succinyl -DHA Functionalized Nanoparticles Efficiently Alleviates Ulcerative Colitis.International journal of nanomedicine · 2024Article
- Review
- Epigenetic and metabolic reprogramming in inflammatory bowel diseases: diagnostic and prognostic biomarkers in colorectal cancer.Cancer cell international · 2023Review
- Gut Barrier Dysfunction and Bacterial Lipopolysaccharides in Colorectal Cancer.Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract · 2023Review
- Aspirin increases chemosensitivity of colorectal cancer cells and inhibits the expression of toll-like receptor 4.Cancer cell international · 2023Article
- Article
- Pou3f1 mediates the effect of Nfatc3 on ulcerative colitis-associated colorectal cancer by regulating inflammation.Cellular & molecular biology letters · 2022Article
- Identification of fatty acid metabolism-related lncRNAs in the prognosis and immune microenvironment of colon adenocarcinoma.Biology direct · 2022Article
- Review
- Neutrophil infiltration combined with necrosis in the primary tumor is a useful prognostic indicator for three-year disease-free survival time in patients with colorectal cancer.Oncology letters · 2022Article
- Lactobacillus coryniformis MXJ32 administration ameliorates azoxymethane/dextran sulfate sodium-induced colitis-associated colorectal cancer via reshaping intestinal microenvironment and alleviating inflammatory response.European journal of nutrition · 2022Article
23 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundColorectal cancer can be efficiently treated when found at early stages, thus the search for novel markers is of paramount importance. Since inflammation is associated with cancer progression and angiogenesis, we investigated expression of cytokines like IL-6 and other mediators that play a key role in the innate immune system, in particular toll like receptor 4 (TLR4), in the microenvironment of lesions from different stages of colon disease progression, from ulcerative colitis to adenoma and adenocarcinoma to find useful markers.
methodsThe presence of inflammatory cells and expression of key cytokines involved in the inflammation process were quantified by immunohistochemistry in specific tissue compartments (epithelial, stromal, endothelial) by immunohistochemistry. A murine azoxymethane/dextran sulfate model in which Tir8, a negative regulator of the inflammatory response, was ablated was used to confirm the clinical observations. 116 Archival tissue samples from patients with different stages of colorectal disease: 13 cases of ulcerative colitis (UC), 34 tubular or tubulo-villous adenomas (AD), and 53 infiltrating adenocarcinomas. 16 specimens of healthy mucosa surgically removed with the cancerous tissue were used as a control.
resultsThe differences between healthy tissues and the diverse lesions was characterized by a marked inflammatory-angiogenic reaction, with significantly (P < 0.05) higher numbers of CD68, CD15, and CD31 expressing cells in all diseased tissues that correlated with increasing grade of malignancy. We noted down-regulation of a potential modulator molecule, Hepatocyte Growth Factor, in all diseased tissues (P < 0.05). TLR-4 and IL6 expression in the tumor microenvironment were associated with adenocarcinoma in human samples and in the murine model. We found that adenocarcinoma patients (pT1-4) with higher TLR-4 expression in stromal compartment had a significantly increased risk in disease progression. In those patients with a diagnosis of pT3 (33 cases) colon cancer, those with very high levels of TLR-4 in the tumor stroma relapsed significantly earlier than those with lower expression levels.
conclusionsThese data suggest that high TLR-4 expression in the tumor microenvironment represents a possible marker of disease progression in colon cancer.
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