Integrins

Sun, Cuicui; Qu, Xian‐Jun; Gao, Zu–Hua

doi:10.1097/cad.0000000000000145

Cited by 29 publications

(7 citation statements)

References 174 publications

(212 reference statements)

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“…The functional role of integrins in tumourigenesis entails more than that of a mechanistic receptor for cell-cell and cell-matrix attachment 36 . Integrin stimulation activates a number of intracellular signalling pathways involved in cell proliferation, differentiation, motility and other essential cell functions 37 and may not always directly correlate with malignant behaviour. Zutter et al .…”

Section: Discussionmentioning

confidence: 99%

Intensified antineoplastic effect by combining an HDAC‐inhibitor, an mTOR‐inhibitor and low dosed interferon alpha in prostate cancer cells

Tsaur

Hudak

Makarević

et al. 2015

J Cellular Molecular Medi

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A significant proportion of men diagnosed with prostate cancer (PCa) eventually develop metastatic disease, which progresses to castration resistance, despite initial response to androgen deprivation. As anticancer therapy has become increasingly effective, acquired drug resistance has emerged, limiting efficacy. Combination treatment, utilizing different drug classes, exemplifies a possible strategy to foil resistance development. The effects of the triple application of the histone deacetylase (HDAC) inhibitor valproic acid (VPA), the mammalian target of rapamycin inhibitor everolimus and low dosed interferon alpha (IFNα) on PCa cell growth and dissemination capacity were investigated. For that purpose, the human PCa cell lines, PC-3, DU-145 and LNCaP were treated with the combined regimen or separate single agents. Cell growth was investigated by the MTT dye reduction assay. Flow cytometry served to analyse cell cycle progression. Adhesion to vascular endothelium or immobilized collagen, fibronectin and laminin was quantified. Migration and invasion characteristics were determined by the modified Boyden chamber assay. Integrin α and β subtypes were investigated by flow cytometry, western blotting and RT-PCR. Integrin related signalling, Epidermal Growth Factor Receptor (EGFr), Akt, p70S6kinase and extracellular signal-regulated kinases (ERK)1/2 activation were also assessed. The triple application of VPA, everolimus and low dosed IFNα blocked tumour cell growth and dissemination significantly better than any agent alone. Antitumour effects were associated with pronounced alteration in the cell cycle machinery, intracellular signalling and integrin expression profile. Combining VPA, everolimus and low dosed IFNα might be a promising option to counteract resistance development and improve outcome in PCa patients.

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Section: Discussionmentioning

confidence: 99%

Intensified antineoplastic effect by combining an HDAC‐inhibitor, an mTOR‐inhibitor and low dosed interferon alpha in prostate cancer cells

Tsaur

Hudak

Makarević

et al. 2015

J Cellular Molecular Medi

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“…The interaction of integrins with the extracellular matrix activates a number of intracellular signaling pathways involved in cell proliferation, differentiation, motility, and other essential cell functions. 100 It has been shown that glioblastoma and its associated vasculature widely express integrins. 3 Preclinical studies have demonstrated that integrin inhibition induces apoptosis of human glioma cells and that integrin inhibitors prolong survival of immunodeficient mice carrying glioma xenografts.…”

Section: Resultsmentioning

confidence: 99%

Molecularly targeted therapies for recurrent glioblastoma: current and future targets

Lau¹,

Magill²,

Aghi³

2014

FOC

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Object Glioblastoma is the most aggressive and diffusely infiltrative primary brain tumor. Recurrence is expected and is extremely difficult to treat. Over the past decade, the accumulation of knowledge regarding the molecular and genetic profile of glioblastoma has led to numerous molecularly targeted therapies. This article aims to review the literature and highlight the mechanisms and efficacies of molecularly targeted therapies for recurrent glioblastoma. Methods A systematic search was performed with the phrase “(name of particular agent) and glioblastoma” as a search term in PubMed to identify all articles published up until 2014 that included this phrase in the title and/or abstract. The references of systematic reviews were also reviewed for additional sources. The review included clinical studies that comprised at least 20 patients and reported results for the treatment of recurrent glioblastoma with molecular targeted therapies. Results A total of 42 articles were included in this review. In the treatment of recurrent glioblastoma, various targeted therapies have been tested over the past 10–15 years. The targets of interest include epidermal growth factor receptor, vascular endothelial growth factor receptor, platelet-derived growth factor receptor, Ras pathway, protein kinase C, mammalian target of rapamycin, histone acetylation, and integrins. Unfortunately, the clinical responses to most available targeted therapies are modest at best. Radiographic responses generally range in the realm of 5%–20%. Progression-free survival at 6 months and overall survival were also modest with the majority of studies reporting a 10%–20% 6-month progression-free survival and 5- to 8-month overall survival. There have been several clinical trials evaluating the use of combination therapy for molecularly targeted treatments. In general, the outcomes for combination therapy tend to be superior to single-agent therapy, regardless of the specific agent studied. Conclusions Recurrent glioblastoma remains very difficult to treat, even with molecular targeted therapies and anticancer agents. The currently available targeted therapy regimens have poor to modest activity against recurrent glioblastoma. As newer agents are actively being developed, combination regimens have provided the most promising results for improving outcomes. Targeted therapies matched to molecular profiles of individual tumors are predicted to be a critical component necessary for improving efficacy in future trials.

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“…Previous studies have identified a linkage between an altered integrin expression, tumor cell progression, metastasis, and chemoresistance [1,5,57]. …”

Section: Discussionmentioning

confidence: 99%

Integrin β1, Osmosensing, and Chemoresistance in Mouse Ehrlich Carcinoma Cells

Sørensen

Rasmussen

Broberg

et al. 2015

Cell Physiol Biochem

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Background/Aims:Altered expression of the integrin family of cell adhesion receptors has been associated with initiation, progression, and metastasis of solid tumors as well as in the development of chemoresistance. Here, we investigated the role of integrins, in particular integrin β₁, in cell volume regulation and drug-induced apoptosis in adherent and non-adherent Ehrlich ascites cell lines. Methods:Adhesion phenotypes were verified by colorimetric cell-adhesion-assay. Quantitative real-time PCR and western blot were used to compare expression levels of integrin subunits. Small interfering RNA was used to silence integrin β₁ expression. Regulatory volume decrease (RVD) after cell swelling was studied with calcein-fluorescence-self-quenching and Coulter counter analysis. Taurine efflux was estimated with tracer technique. Caspase assay was used to determine apoptosis. Results:We show that adherent cells have stronger fibronectin binding and a significantly increased expression of integrin α₅, α_v, and β₁ at mRNA and protein level, compared to non-adherent cells. Knockdown of integrin β₁ reduced RVD of the adherent but not of the non-adherent cells. Efflux of taurine was unaffected. In contrast to non-adherent, adherent cells exhibited chemoresistance to chemotherapeutic drugs (cisplatin and gemcitabine). However, knockdown of integrin β₁ promoted cisplatin-induced caspase activity in adherent cells. Conclusion:Our data identifies integrin β₁ as a part of the osmosensing machinery and regulator of cisplatin resistance in adherent Ehrlich cells.

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Integrins

Cited by 29 publications

References 174 publications

Intensified antineoplastic effect by combining an HDAC‐inhibitor, an mTOR‐inhibitor and low dosed interferon alpha in prostate cancer cells

Intensified antineoplastic effect by combining an HDAC‐inhibitor, an mTOR‐inhibitor and low dosed interferon alpha in prostate cancer cells

Molecularly targeted therapies for recurrent glioblastoma: current and future targets

Integrin β1, Osmosensing, and Chemoresistance in Mouse Ehrlich Carcinoma Cells

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