Correlation between Beta1 integrin expression and prognosis in clinically localized prostate cancer

Pontes‐Júnior, José; Reis, Sabrina T.; Bernardes, Felipe; Oliveira, Luiz Carlos Neves de; Barros, Érika Aparecida Felix de; Dall’Oglio, Marcos F.; Timosczuk, Luciana M. S.; Ribeiro-Filho, Leopoldo; Srougi, Miguel; Leite, Kátia R. M.

doi:10.1590/s1677-5538.ibju.2013.03.06

Cited by 12 publications

(6 citation statements)

References 26 publications

(27 reference statements)

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“…Similar to the controversy concerning metastasis, the associations between β1 integrin and the clinical features of patients are unclear. In certain types of cancer, β1 integrin is associated with poor prognosis or metastasis, including in prostatic cancer (15,24), melanoma (25), gastric carcinoma (26) and hypopharyngeal squamous cell carcinoma (27). However, in other types of cancer, including breast cancer, studies have reported different or contradictory conclusions (28)(29)(30).…”

Section: Metastasismentioning

confidence: 99%

β1 and β3 integrins in breast, prostate and pancreatic cancer: A novel implication (Review)

et al. 2018

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Abstract.Integrins are transmembrane glycoproteins that consist of an α and a β subunit. Specific integrin heterodimers preferentially bind to distinct extracellular matrix (ECM) proteins to affect the characteristics of cells or the components of the ECM. Among the different integrins, β1 and β3 integrins serve essential roles in the progression of different cancer-associated processes, including the initiation, proliferation, survival, migration and invasion. Furthermore, previous studies have revealed a ratio between these two integrins in cancer cells, which also demonstrated that the functions of these two integrins are paradoxical. This indicated that the proliferation and metastasis of cancer cells are not always parallel and may be considered independently maintained. Additionally, the present review may assist in understanding certain aspects of cancer, and in making clinical decisions in a novel and more comprehensive manner. IntroductionIntegrins are transmembrane glycoproteins that consist of an α subunit and a β subunit. A total of eight different β subunits may dimerize, in limited combinations, with 18α subunits to form ≥24 distinct integrins (1,2). Specific integrin heterodimers preferentially bind to distinct extracellular matrix (ECM) proteins. Integrins may bind the ligands in ECM directly, including fibronectin and laminin, to affect the characteristics of cells or the components of ECM. Regarding cancer cells, integrins serve roles in numerous aspects, including proliferation, survival, migration and invasion (1).Integrins primarily affect cells in two ways, the first is through binding with proteins directly, including talin, vinculin and filamin, which may regulate the actin cytoskeleton of cells (3). The other is by phosphorylating the relative kinases, including focal adhesion kinases (FAKs), proto-oncogene tyrosine-protein kinase (Src)-family kinases (SFKs) and integrin-linked kinase (ILK), to activate or cooperate with the other cell signaling pathways (1,4). Additionally, integrin clustering on the cell surface and trafficking from the endosomes may affect the ligand affinity and quantity of the protein on cell surface (5-7).Among the different integrins, β1 and β3 integrins serve essential roles in the progression of different types of cancer (1,2). Furthermore, previous studies investigating the association between these two integrins have demonstrated many different perspectives (8-11), together providing a novel and more comprehensive understanding of cancer. Functions of β1 integrin in cancerIn tumors, the β1 subunit of integrin may combine with different α subunits, including α4, α5 and α2, to affect the characteristics of cancer cells, and the progression of tumors (1). The primary function of β1 integrin is to form focal adhesion between cancer cells and ECM. This adhesion is the basis for the survival of cancer cells and is also associated with their migratory and metastatic capabilities (2). There are series of proteins in the cytoplasm, including talin, kindlin and ILK, ...

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Section: Metastasismentioning

confidence: 99%

β1 and β3 integrins in breast, prostate and pancreatic cancer: A novel implication (Review)

et al. 2018

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“… 13 – 17 Other studies have also shown that, in many cancer types, ITGB1 may induce resistance to radiotherapies, chemotherapies, and targeted therapies. 18 – 22 On the basis of these findings, ITGB1 has been studied extensively in terms of the biology of solid tumors, and its aberrant expression at the protein or RNA level has been shown to correlate with poor prognosis in several types of cancer, including lung cancer, 23 – 26 gastric cancer, 27 breast cancer, 28 – 30 prostate cancer, 31 pancreatic carcinoma, 32 , 33 and colorectal cancer, 34 , 35 making it a potential target for antitumor therapies. Nevertheless, the prognostic significance of ITGB1 expression in patients with cancer remains inconsistent.…”

Section: Introductionmentioning

confidence: 99%

Prognostic value of increased integrin-beta 1 expression in solid cancers: a meta-analysis

Sun¹,

Zhou²,

Ma³

et al. 2018

OTT

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Integrin-beta 1 (ITGB1) is aberrantly overexpressed or downregulated in solid cancers; however, its prognostic value remains controversial. Therefore, we conducted a meta-analysis to explore whether ITGB1 expression is correlated with overall survival (OS) and the clinicopathological characteristics of patients with solid cancers. We systematically searched the PubMed, Embase, and Web of Science databases for eligible studies published up to June 1, 2017. In total, 22 studies involving 3,666 patients were included. A sensitivity analysis was performed to assess the validity and reliability of the pooled OS. Among the 22 studies, 7 focused on lung cancer, 3 focused on colorectal cancer, 6 focused on breast cancer, 3 involved melanoma, and 3 involved pancreatic cancer. The pooled results showed that high ITGB1 expression was significantly associated with worse OS in lung cancer (pooled hazard ratio [HR]=1.78, 95% CI: 1.19–2.65, p<0.05) and breast cancer (pooled HR=1.88, 95% CI: 1.46–2.42, p<0.01). In addition, a significant association was observed between high ITGB1 expression and disease-free survival in breast cancer (pooled HR=1.63, 95% CI: 1.17–2.25, p<0.001) and pancreatic cancer (pooled HR=2.49, 95% CI: 1.35–4.61, p<0.001). However, high ITGB1 expression was not related to OS in colorectal cancer, pancreatic cancer, or melanoma. The pooled HRs used to evaluate the prognostic value of increased ITGB1 expression in lung cancer, breast cancer, and pancreatic cancer were not significantly altered, which indicates that the pooled results were robust. The results of this study indicate that the prognostic value of decreased ITGB1 expression varies among solid cancers.

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“…The overexpression of α v β 3 , α v β 5 and α 5 β 1 integrins on cancer cells, neovasculature and metastatic sites has been confirmed in many human malignancies, and changes in integrin expression and function are associated with disease progression. 26 , 27 , 36 Integrins are validated targets for RGD peptide ligands and several nanoparticle systems carrying these peptides are under development. Here we describe the development and testing of integrin-targeted PVX nanofilaments modified with cyclic RGD peptides.…”

Section: Introductionmentioning

confidence: 99%

To Target or Not to Target: Active vs. Passive Tumor Homing of Filamentous Nanoparticles Based on Potato virus X

et al. 2015

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Nanoparticles are promising platforms for the diagnosis and treatment of cancer. Diverse classes and shapes of materials have been investigated to establish design principles that achieve the effective partitioning of medical cargos between tumors and healthy tissues. Molecular targeting strategies combined with specific nanoparticle shapes confer tissue-specificity on the carriers, allowing the cell-specific delivery of cargos. We recently developed a filamentous platform technology in which the plant virus Potato virus X (PVX) was used as a scaffold. These particles are flexible 515 × 13 nm filaments that encourage passive tumor homing. Here we sought to advance the PVX platform by including a molecular targeting strategy based on cyclic RGD peptides, which specifically bind to integrins upregulated on tumor cells, neovasculature, and metastatic sites. Although the RGD-targeted filaments outperformed the PEGylated stealth filaments in vitro, enhanced tumor cell targeting did not translate into improved tumor homing in vivo in mouse tumor models. The RGD-PVX and PEG-PVX filaments showed contrasting biodistribution profiles. Both formulations were cleared by the liver and spleen, but only the stealth filaments accumulated in tumors, whereas the RGD-targeted filaments were sequestered in the lungs. These results provide insight into the design principles for virus-based nanoparticles that promote the delivery of medical cargos to the appropriate cell types.

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Correlation between Beta1 integrin expression and prognosis in clinically localized prostate cancer

Cited by 12 publications

References 26 publications

β1 and β3 integrins in breast, prostate and pancreatic cancer: A novel implication (Review)

β1 and β3 integrins in breast, prostate and pancreatic cancer: A novel implication (Review)

Prognostic value of increased integrin-beta 1 expression in solid cancers: a meta-analysis

To Target or Not to Target: Active vs. Passive Tumor Homing of Filamentous Nanoparticles Based on Potato virus X

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