Serum Trefoil Factors in Patients with Inflammatory Bowel Disease

Grønbæk, Henning; Vestergaard, Else Marie; Hey, Henrik; Nielsen, Joachim; Nexø, Ebba

doi:10.1159/000096591

Cited by 41 publications

(28 citation statements)

References 54 publications

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“…Trefoil factor 1 is a secreted protein that is involved in various pathological condition including inflammatory bowel disease, 22 prostate cancer, 23 breast cancer, 24 and lung cancer. 25 Because our microarray and immunohistochemistry data indicated that TFF1 expression was specific to pancreatic cancer when compared with normal tissue and pancreatitis, we measured TFF1 in pancreatic cancer cell conditioned media.…”

Section: Discussionmentioning

confidence: 99%

Trefoil Factor 1 Stimulates Both Pancreatic Cancer and Stellate Cells and Increases Metastasis

Arumugam¹,

Brandt²,

Ramachandran³

et al. 2011

Pancreas

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Objectives Trefoil factor 1 (TFF1) is a stable secretory protein expressed widely in the gastrointestinal mucosa that is also expressed in pancreatic ductal adenocarcinoma (PDAC). In the current study, we documented the extent and timing of TFF1 expression and investigated the effects of TFF1 on PDAC cells and stellate cells, the primary cells of the PDAC stroma. Methods Trefoil factor 1 expression in pancreatic cancer tissues and cell lines was analyzed using microarray, quantitative reverse transcriptase–polymerase chain reaction, and immunohistochemistry. The effects of recombinant TFF1 on cell growth, migration, and invasion of pancreatic cancer cell lines and immortalized human pancreatic stellate cells (HPSCs) were analyzed using MTS and Matrigel-coated invasion chambers. In vivo studies were also conducted in which Mpanc-96 cells stably expressing TFF1 were implanted orthotopically into nude mice. Results Trefoil factor 1 was highly increased in preneoplastic lesions. Recombinant TFF1 stimulated motility of both cancer and HPSCs. In contrast, only HPSC cell growth was increased by TFF1. In vivo studies showed that overexpression of TFF1 in PDAC cells did not affect primary tumor growth but greatly increased metastasis. Conclusions The present data demonstrate that TFF1 influences both PDAC cells and stellate cells and stimulates metastasis.

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Section: Discussionmentioning

confidence: 99%

Trefoil Factor 1 Stimulates Both Pancreatic Cancer and Stellate Cells and Increases Metastasis

Arumugam¹,

Brandt²,

Ramachandran³

et al. 2011

Pancreas

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“…The TFF3 gene, which plays a role in mucosal protection and repair in the gastrointestinal tract, is known to be induced by estrogen [42], and it is over-expressed in several types of cancer [43]. Elevated serum levels of TFF3 have been reported in inflammatory bowel disease [44] and ulceration of the upper gastrointestinal tract [45]. LGALS1 was shown to be induced by estrogen [46].…”

Section: Discussionmentioning

confidence: 99%

Application of serum proteomics to the Women's Health Initiative conjugated equine estrogens trial reveals a multitude of effects relevant to clinical findings

et al. 2009

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BackgroundThe availability of serum collections from the Women's Health Initiative (WHI) conjugated equine estrogens (CEE) randomized controlled trial provides an opportunity to test the potential of in-depth quantitative proteomics to uncover changes in the serum proteome related to CEE and to assess their relevance to trial findings, including elevations in the risk of stroke and venous thromboembolism and a reduction in fractures.MethodsFive independent large scale quantitative proteomics analyses were performed, each comparing a set of pooled serum samples collected from 10 subjects, 1 year following initiation of CEE at 0.625 mg/d, relative to their baseline pool. A subset of proteins that exhibited increased levels with CEE by quantitative proteomics was selected for validation studies.ResultsOf 611 proteins quantified based on differential stable isotope labeling, the levels of 116 (19%) were changed after 1 year of CEE (nominal P < 0.05), while 64 of these had estimated false discovery rates <0.05. Most of the changed proteins were not previously known to be affected by CEE and had relevance to processes that included coagulation, metabolism, osteogenesis, inflammation, and blood pressure maintenance. To validate quantitative proteomic data, 14 proteins were selected for ELISA. Findings for ten - IGF1, IGFBP4, IGFBP1, IGFBP2, F10, AHSG, GC, CP, MMP2, and PROZ - were confirmed in the initial set of 50 subjects and further validated in an independent set of 50 additional subjects who received CEE.ConclusionsCEE affected a substantial fraction of the serum proteome, including proteins with relevance to findings from the WHI CEE trial related to cardiovascular disease and fracture.Clinical Trials RegistrationClinicalTrials.gov identifier: NCT00000611

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“…They facilitate epithelial cell migration to cover damaged areas, constrain proapoptotic signals and promote angiogenesis and leukocyte migration. TFF peptipes have been mostly studied in the gastrointestinal tract and its associated diseases of chronic inflammation such as inflammatory bowel disease, where upregulation of TFF peptides has been demonstrated [16,19]. …”

Section: Discussionmentioning

confidence: 99%

“…A non-significant trend towards increased urinary TFF2 levels in early CKD stages compared to controls was noticed and may reflect the described initial repair response and immediate clearance. In the gastrointestinal tract higher TFF peptide levels are associated with ulceration and inflammation and can be correlated with disease activity [16,19]. Similarly, TFF2 upregulation in chronic renal failure might occur to limit cell death and epithelial damage.…”

Section: Discussionmentioning

confidence: 99%

Increased trefoil factor 2 levels in patients with chronic kidney disease

et al. 2017

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In chronically damaged tissue, trefoil factor family (TFF) peptides ensure epithelial protection and restitution. In chronic kidney disease (CKD), TFF1 and TFF2 are reported to be upregulated. Especially in the early phase, CKD is associated with silently ongoing renal damage and inflammation. Moreover, many patients are diagnosed late during disease progression. We therefore sought to investigate the potential of TFF2 as biomarker for CKD. We followed 118 patients suffering from predialysis CKD and 23 healthy volunteers. TFF2 concentrations were measured using ELISA. Our results showed, that median TFF2 serum levels were significantly higher in patients with later CKD stages as compared to healthy controls (p < 0.001) or early stages (p < 0.001). In patients with mid CKD stages TFF2 serum levels were significantly higher than in healthy controls (p = 0.002). Patients with early or mid CKD stages had significantly higher TFF2 urine concentrations than later CKD stages (p < 0.001 and p = 0.009, respectively). Fractional TFF2 excretion differed significantly between early CKD stages and healthy controls (p = 0.01). ROC curve showed that TFF2 levels can predict different CKD stages (AUC > 0.75). In conclusion, urine and serum TFF2 levels of CKD patients show a different profile dependent on CKD stages. Whereas TFF2 urine levels continuously decreased with disease progression, TFF2 serum concentrations progressively increased from the early to later CKD stages, indicating changes in renal function and offering the potential to examine the course of CKD.

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Serum Trefoil Factors in Patients with Inflammatory Bowel Disease

Cited by 41 publications

References 54 publications

Trefoil Factor 1 Stimulates Both Pancreatic Cancer and Stellate Cells and Increases Metastasis

Trefoil Factor 1 Stimulates Both Pancreatic Cancer and Stellate Cells and Increases Metastasis

Application of serum proteomics to the Women's Health Initiative conjugated equine estrogens trial reveals a multitude of effects relevant to clinical findings

Increased trefoil factor 2 levels in patients with chronic kidney disease

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