Trefoil Factor Family–Peptides Promote Migration of Human Bronchial  Epithelial Cells

Oertel, Martin; Graneß, Angela; Thim, Lars; Bühling, Frank; Kalbacher, Hubert; Hoffmann, Werner

doi:10.1165/ajrcmb.25.4.4429

Cited by 100 publications

(98 citation statements)

References 52 publications

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“…The expression of these candidate downstream genes, found in mammalian lung tissue (33,34), has been reported to be upregulated by GATA transcription factors (35). Akiyama et al (7), using demethylation agents, re-expressed not only GATA-4 and GATA-5 in neoplastic cell lines but also their downstream targets including TFF1, TFF2, TFF3, and inhibin-␣.…”

Section: Gata-4 (%)mentioning

confidence: 99%

Hypermethylation of the GATA Genes in Lung Cancer

Guo

Akiyama

House

et al. 2004

Clinical Cancer Research

113

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Purpose: In lung cancer, DNA hypermethylation is known to be a common event.Experimental Design: Gene expression and methylation status of GATA-4, GATA-5, and GATA-6 were analyzed with cell lines and primary human lung cancers. Methylation profiles of primary lung cancers were analyzed and correlated with clinical as well as histopathological data.Results: Complete methylation was detected by methylation-specific PCR for both GATA-4 and GATA-5 in four cell lines (H358, DMS-53, A549, and H1299), all of which had no expression by reverse transcription-PCR analysis. Demethylation with 5-aza-2deoxycytidine restored expression in each case. GATA-6 was ubiquitously expressed in all of the six cell lines. GATA-4 bisulfite sequencing revealed complete methylation of the GATA-4 promoter in H358 cells, correlating well with its lack of expression at the mRNA level. Only a few CpG sites showed methylation by bisulfite sequencing within the GATA-4 promoter in a cell line that expressed the gene. In 63 cases of primary lung cancers, GATA-4 and GATA-5 promoter methylation was detected in (42 of 63) 67% and (26 of 63) 41%, respectively. GATA-6 remained unmethylated both in cell lines and primary tumors. Six autopsy specimens of normal lung tissue showed no aberrant promoter hypermethylation for the GATA genes. Correlation of concomitant GATA-4 and GATA-5 methylation with clinicopathological parameters only found a statistically significant increase in methylation frequency with increasing patient age (P < 0.001).Conclusions: These epigenetic changes in the GATA genes in lung cancer are tumor-specific, relate to the loss of GATA gene expression, and occur increasingly in the elderly.

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Section: Gata-4 (%)mentioning

confidence: 99%

Hypermethylation of the GATA Genes in Lung Cancer

Guo

Akiyama

House

et al. 2004

Clinical Cancer Research

113

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“…The trefoil factor (TFF) family members TFF1, TFF2 and TFF3 are secreted from a variety of mucous epithelial tissues and function as important regulators of cell migration, immune reaction, mucosa repair, angiogenesis and tumorigenesis (14)(15)(16). TFF peptides have also been identified in many other organs, including the respiratory tract, gallbladder, prostate, uterus, thyroid gland, salivary glands, mammary glands and the nervous system (17).…”

Section: Introductionmentioning

confidence: 99%

Expression of Clara cell 10-kDa protein and trefoil factor family 1 in patients with chronic rhinosinusitis and nasal polyps

Wang

2018

Exp Ther Med

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Abstract. The current study measured the expression of Clara cell 10-kDa protein (CC10) and trefoil factor family 1 (TFF1) in the sinus mucosa of patients exhibiting chronic rhinosinusitis (CRS) and nasal polyps (NP). CC10 and TFF1 expression in the sinus mucosa of the control group and patients with CRS and NP was determined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blotting and immunohistochemistry. The correlation between CC10 and TFF1 expression was further analyzed using Spearman's correlation analysis. The expression of TFF1 was significantly increased in the sinus mucosa of patients with CRS and NP, whereas CC10 expression was significantly decreased compared with controls. Spearman's correlation analysis identified a negative correlation between CC10 and TFF1 expression in the sinus mucosa of patients with CRS and NP. The results of immunohistochemistry and RT-qPCR were consistent with each other. Hematoxylin and eosin staining revealed notable lesions in the mucous membranes, goblet cells and cilia of sinus mucosa samples from patients with CRS and NP. The negative correlation between CC10 and TFF1 expression during the progression of CRS and NP suggest that CC10 and TFF1 may serve important roles in its pathogenesis.

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“…Experimental induction of ulceration in the rat stomach leads to rapid up-regulation of TFF2 expression with high levels observed 30 min after ulceration with persistence for up to 10 days (1). TFF2 is secreted into the mucus layer of the gastrointestinal tract of mammals where it stabilizes the mucin gel layer and stimulates migration of epithelial cells (2)(3)(4), suggesting an important role in restitution and in maintenance of the integrity of the gut. Exogenous administration of recombinant TFF2, either orally or intravenously, provides mucosal protection in several rodent models of acute gastric or intestinal injury (5,6).…”

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confidence: 99%

Secreted Trefoil Factor 2 Activates the CXCR4 Receptor in Epithelial and Lymphocytic Cancer Cell Lines

Dubeykovskaya

Dubeykovskiy

Solal-Cohen

et al. 2009

Journal of Biological Chemistry

106

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The secreted trefoil factor family 2 (TFF2) protein contributes to the protection of the gastrointestinal mucosa from injury by strengthening and stabilizing mucin gels, stimulating epithelial restitution, and restraining the associated inflammation. Although trefoil factors have been shown to activate signaling pathways, no cell surface receptor has been directly linked to trefoil peptide signaling. Here we demonstrate the ability of TFF2 peptide to activate signaling via the CXCR4 chemokine receptor in cancer cell lines. We found that both mouse and human TFF2 proteins (at ϳ0.5 M) activate Ca 2؉ signaling in lymphoblastic Jurkat cells that could be abrogated by receptor desensitization (with SDF-1␣) or pretreatment with the specific antagonist AMD3100 or an anti-CXCR4 antibody. TFF2 pretreatment of Jurkat cells decreased Ca 2؉ rise and chemotactic response to SDF-1␣. In addition, the CXCR4-negative gastric epithelial cell line AGS became highly responsive to TFF2 treatment upon expression of the CXCR4 receptor. TFF2-induced activation of mitogen-activated protein kinases in gastric and pancreatic cancer cells, KATO III and AsPC-1, respectively, was also dependent on the presence of the CXCR4 receptor. Finally we demonstrate a distinct proliferative effect of TFF2 protein on an AGS gastric cancer cell line that expresses CXCR4. Overall these data identify CXCR4 as a bona fide signaling receptor for TFF2 and suggest a mechanism through which TFF2 may modulate immune and tumorigenic responses in vivo.

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Trefoil Factor Family–Peptides Promote Migration of Human Bronchial Epithelial Cells

Cited by 100 publications

References 52 publications

Hypermethylation of the GATA Genes in Lung Cancer

Hypermethylation of the GATA Genes in Lung Cancer

Expression of Clara cell 10-kDa protein and trefoil factor family 1 in patients with chronic rhinosinusitis and nasal polyps

Secreted Trefoil Factor 2 Activates the CXCR4 Receptor in Epithelial and Lymphocytic Cancer Cell Lines

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