Expression of Toll-like receptor 4 and beta 1 integrin in breast cancer

Petričević, Branka; Vrbanec, Damir; Jakić-Razumović, Jasminka; Brčić, Iva; Rabić, Domagoj; Badovinac, Tomislav; Ozimec, Elizabeta; Bali, Vedrana

doi:10.1007/s12032-011-9885-0

Cited by 22 publications

(23 citation statements)

References 47 publications

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“…In conclusion, our results suggest that the SPA4 peptide has potential to be further developed as an immunotherapeutic strategy to limit inflammation-induced cancer. It is expected that SPA4 peptide may be of clinical utility in other types of cancer where the activation of TLR4 has been shown to exert oncogenic effects 32 , 33 , 44 , 45 …”

Section: Discussionmentioning

confidence: 99%

A TLR4-interacting peptide inhibits lipopolysaccharide-stimulated inflammatory responses, migration and invasion of colon cancer SW480 cells

et al. 2012

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Inflammation is a major risk factor for carcinogenesis in patients affected by chronic colitis, yet the molecular mechanisms underlying the progression from chronic inflammation to cancer are not completely understood. Activation of the Toll-like receptor 4 (TLR4)-NFκB signaling axis is associated with inflammation. Thus, we hypothesized that inhibition of TLR4-NFκB signaling might help in limiting inflammatory responses and inflammation-induced oncogenesis. In this work, we studied the effects of a TLR4-interacting surfactant protein A-derived (SPA4) peptide on lipopolysaccharide (LPS)-induced TLR4-NFκB signaling and cancer progression. We first characterized this peptide for its ability to bind the TLR4 ligand-LPS and for physico-chemical characteristics. Inflammation was induced by challenging the colon cancer SW480 cells with Escherichia coli LPS. Cells were then treated with varying amounts of the SPA4 peptide. Changes in the expression of TLR4, interleukin (IL)-1β and IL-6, in intracellular NFκB-related signal transducers (IKBα, p65, phosphorylated IKBα, phosphorylated p65, RelB, COX-2) as well as in the transcriptional activity of NFκB were studied by immunocytochemistry, immunoblotting and NFκB reporter assay, respectively. Simultaneously, the effects on LPS-induced cell migration and invasion were determined. We found that the SPA4 peptide does not bind to LPS. Rather, its binding to TLR4 inhibits the LPS-induced phosphorylation of p65, production of IL-1β and IL-6, activity of NFκB, migration and invasion of SW480 cells. In conclusion, our results suggest that the inhibition of TLR4-NFκB signaling by a TLR4-binding peptide may help for the treatment of chronic inflammation and prevention of inflammation-induced cancer in patients with colitis.

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Section: Discussionmentioning

confidence: 99%

A TLR4-interacting peptide inhibits lipopolysaccharide-stimulated inflammatory responses, migration and invasion of colon cancer SW480 cells

et al. 2012

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“…For statistical analysis we used the same method established by Petricevic and colleagues [21] where the results were presented as a positive (strong positive staining 3+ and moderately positive staining 2+) or a negative (weak positive 1+ and negative staining 0) for tumor cells.…”

Section: Methodsmentioning

confidence: 99%

Beta 1 integrin predicts survival in breast cancer: a clinicopathological and immunohistochemical study

et al. 2012

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BackgroundThe main focus of several studies concerned with cancer progression and metastasis is to analyze the mechanisms that allow cancer cells to interact and quickly adapt with their environment. Integrins, a family of transmembrane glycoproteins, play a major role in invasive and metastatic processes. Integrins are involved in cell adhesion in both cell-extracellular matrix and cell-cell interactions, and particularly, β1 integrin is involved in proliferation and differentiation of cells in the development of epithelial tissues. This work aimed to investigate the putative role of β1 integrin expression on survival and metastasis in patients with breast invasive ductal carcinoma (IDC). In addition, we compared the expression of β1 integrin in patients with ductal carcinoma in situ (DCIS).MethodsThrough tissue microarray (TMA) slides containing 225 samples of IDC and 67 samples of DCIS, β1 integrin expression was related with several immunohistochemical markers and clinicopathologic features of prognostic significance.Resultsβ1 integrin was overexpressed in 32.8% of IDC. In IDC, β1 integrin was related with HER-2 (p = 0.019) and VEGF (p = 0.011) expression and it had a significant relationship with metastasis and death (p = 0.001 and p = 0.05, respectively). Kaplan-Meier survival analysis showed that the overexpression of this protein is very significant (p = 0.002) in specific survival (number of months between diagnosis and death caused by the disease). There were no correlation between IDC and DCIS (p = 0.559) regarding β1 integrin expression.ConclusionsConsidering that the expression of β1 integrin in breast cancer remains controversial, specially its relation with survival of patients, our findings provide further evidence that β1 integrin can be a marker of poor prognosis in breast cancer.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/6652215267393871

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“…This is highly pertinent given that protein function and protein localisation are closely correlated. Studies have also shown that accounting for protein localisation can be an essential requirement to identifying correlations with other proteins when applying the IHC technique [48]. To date, very few studies have evaluated the prognostic significance of differential protein distribution within diagnostic breast cancer tissue samples.…”

Section: Discussionmentioning

confidence: 99%

Differential subcellular and extracellular localisations of proteins required for insulin-like growth factor- and extracellular matrix-induced signalling events in breast cancer progression

et al. 2014

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BackgroundCancer metastasis is the main contributor to breast cancer fatalities as women with the metastatic disease have poorer survival outcomes than women with localised breast cancers. There is an urgent need to develop appropriate prognostic methods to stratify patients based on the propensities of their cancers to metastasise. The insulin-like growth factor (IGF)-I: IGF binding protein (IGFBP):vitronectin complexes have been shown to stimulate changes in gene expression favouring increased breast cancer cell survival and a migratory phenotype. We therefore investigated the prognostic potential of these IGF- and extracellular matrix (ECM) interaction-induced proteins in the early identification of breast cancers with a propensity to metastasise using patient-derived tissue microarrays.MethodsSemiquantitative immunohistochemistry analyses were performed to compare the extracellular and subcellular distribution of IGF- and ECM-induced signalling proteins among matched normal, primary cancer and metastatic cancer formalin-fixed paraffin-embedded breast tissue samples.ResultsThe IGF- and ECM-induced signalling proteins were differentially expressed between subcellular and extracellular localisations. Vitronectin and IGFBP-5 immunoreactivity was lower while β1 integrin immunoreactivity was higher in the stroma surrounding metastatic cancer tissues, as compared to normal breast and primary cancer stromal tissues. Similarly, immunoreactive stratifin was found to be increased in the stroma of primary as well as metastatic breast tissues. Immunoreactive fibronectin and β1 integrin was found to be highly expressed at the leading edge of tumours. Based on the immunoreactivity it was apparent that the cell signalling proteins AKT1 and ERK1/2 shuffled from the nucleus to the cytoplasm with tumour progression.ConclusionThis is the first in-depth, compartmentalised analysis of the distribution of IGF- and ECM-induced signalling proteins in metastatic breast cancers. This study has provided insights into the changing pattern of cellular localisation and expression of IGF- and ECM-induced signalling proteins in different stages of breast cancer. The differential distribution of these biomarkers could provide important prognostic and predictive indicators that may assist the clinical management of breast disease, namely in the early identification of cancers with a propensity to metastasise, and/or recur following adjuvant therapy.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2407-14-627) contains supplementary material, which is available to authorized users.

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Expression of Toll-like receptor 4 and beta 1 integrin in breast cancer

Cited by 22 publications

References 47 publications

A TLR4-interacting peptide inhibits lipopolysaccharide-stimulated inflammatory responses, migration and invasion of colon cancer SW480 cells

A TLR4-interacting peptide inhibits lipopolysaccharide-stimulated inflammatory responses, migration and invasion of colon cancer SW480 cells

Beta 1 integrin predicts survival in breast cancer: a clinicopathological and immunohistochemical study

Differential subcellular and extracellular localisations of proteins required for insulin-like growth factor- and extracellular matrix-induced signalling events in breast cancer progression

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