Abituzumab Targeting of αV-Class Integrins Inhibits Prostate Cancer Progression

Jiang, Yuan; Dai, Jinlu; Yao, Zhi; Shelley, Greg; Keller, Evan T.

doi:10.1158/1541-7786.mcr-16-0447

Cited by 31 publications

(24 citation statements)

References 26 publications

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“…Parental (MDA-MB-231) and brain metastatic cells (MDA-MB-231BR) do not exhibit differences in proliferation, although MDA-MB- 231BR showed a 2.5-fold increase in βIII-tubulin protein levels (47). Jiang et al (48) also demonstrated that targeting αv integrin with abitumumab inhibited prostate cancer cell adhesion, migration and invasion, but not proliferation in vitro . MicroRNA-124 inhibited hepatocarcinoma cell invasion and migration by suppressing αv integrin (49).…”

Section: Discussionmentioning

confidence: 98%

High αv Integrin Level of Cancer Cells Is Associated with Development of Brain Metastasis in Athymic Rats

Pagel

Muldoon

et al. 2017

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Background/Aim Brain metastases commonly occur in patients with malignant skin, lung and breast cancers resulting in high morbidity and poor prognosis. Integrins containing an αv subunit are cell adhesion proteins that contribute to cancer cell migration and cancer progression. We hypothesized that high expression of αv integrin cell adhesion protein promoted metastatic phenotypes in cancer cells. Materials and Methods Cancer cells from different origins were used and studied regarding their metastatic ability and intetumumab, anti-αv integrin mAb, sensitivity using in vitro cell migration assay and in vivo brain metastases animal models. Results The number of brain metastases and the rate of occurrence were positively correlated with cancer cell αv integrin levels. High αv integrin-expressing cancer cells showed significantly faster cell migration rate in vitro than low αv integrin-expressing cells. Intetumumab significantly inhibited cancer cell migration in vitro regardless of αv integrin expression level. Overexpression of αv integrin in cancer cells with low αv integrin level accelerated cell migration in vitro and increased the occurrence of brain metastases in vivo. Conclusion αv integrin promotes brain metastases in cancer cells and may mediate early steps in the metastatic cascade, such as adhesion to brain vasculature. Targeting αv integrin with intetumumab could provide clinical benefit in treating cancer patients who develop metastases.

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Section: Discussionmentioning

confidence: 98%

High αv Integrin Level of Cancer Cells Is Associated with Development of Brain Metastasis in Athymic Rats

Pagel

Muldoon

et al. 2017

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“…Considered a good prognostic indicator, integrin ␣v␤ 6 is upregulated in various cancer types in inverse correlation with the patients' survival time (47). As of now, antagonists to integrin ␣v in the form of monoclonal antibodies have been successfully employed to halt melanoma and prostate cancer progression in vivo (48)(49)(50). Cilengitide, a cyclic RGD pentapeptide that selectively binds to and inhibits ␣v integrins, has even made it to phase III clinical trials (51).…”

Section: Discussionmentioning

confidence: 99%

Translocating a High-Affinity Designer TIMP-1 to the Cell Membrane for Total Renal Carcinoma Inhibition: Putting the Prion Protein to Good Use

Jiang

Zhang

et al. 2019

Molecular and Cellular Biology

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Membrane type 1-matrix metalloproteinase (MT1-MMP) and tumor necrosis factor α (TNF-α)-converting enzyme (TACE) are prominent membrane-anchored metalloproteinases that regulate the turnover of extracellular matrix (ECM) components and bioactive molecules required for cancer proliferation. In this study, we describe a novel approach that would allow tissue inhibitor of metalloproteinase 1 (TIMP-1), the endogenous inhibitor of the matrix metalloproteinases (MMPs), to be translocated to the cell membrane for simultaneous MT1-MMP/TACE inhibition. We achieve this by fusing T1TACE, a designer TIMP-1 with superb affinities for MT1-MMP and TACE, to the glycosyl-phosphatidyl inositol anchor of prions to create a membrane-tethered, broad-spectrum inhibitor, named T1Pr αTACE, that colocalizes with MT1-MMP and TACE on the cell surface. Transduction of T1Pr αTACE in human fibrosarcoma cells results not only in a substantial reduction in gelatinolytic and TNF-α/heparin binding epithelial growth factor shedding activities but also in a loss of tubulogenic capability in three-dimensional matrices. In renal carcinoma, T1Pr αTACE triggers cellular senescence and disrupts MMP-mediated proteolysis of ECM components such as fibronectin and collagen I, leading to an impairment in cell motility and survival under both in vitro and in vivo conditions. Taken together, our findings may provide a new perspective in TIMP targeting that could be exploited to halt metastatic renal carcinoma progression.

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“…d -pinitol downregulates αvβ3 integrin expression through two important pathways. First, this compound inhibits the FAK/c-Src kinase phosphorylation pathway, which plays an important role in cell motility and invasion in a dose-dependent manner [ 9 , 13 ]. Second, d -pinitol decreases p65 phosphorylation in the NF-κB signal transduction pathway [ 9 ].…”

Section: Natural Herbs Inhibit α2β1 and αVβ3 Integrinsmentioning

confidence: 99%

“…Integrins that contain the αv subunit contribute too many cellular functions that have been shown to promote malignancies, such as melanoma, renal cancer, colorectal cancer, and PCa [ 13 ]. Inhibition of αv integrin activation has been shown to reduce cell survival and induce cell cycle blockade [ 13 ]. This study also showed that this also reduced tumor growth and metastasis, thereby providing the desired antitumor effect.…”

Section: Monoclonal Antibodies Inhibit αV and β1 Integrinmentioning

confidence: 99%

“…On the other hand, β1 integrins are highly expressed in the basal cell layer and are localized in the basal cell/stromal interface, where integrins interact with the ECM [ 13 ]. The activation of β1 integrins play a critical role in PCa metastasis potential by increasing their resistance to cell death [ 14 ].…”

Section: Monoclonal Antibodies Inhibit αV and β1 Integrinmentioning

confidence: 99%

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Integrin Inhibitors in Prostate Cancer

Juan-Rivera

Martínez‐Ferrer

2018

Cancers

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Prostate cancer (PCa) is the most frequently diagnosed cancer and the third highest cause of cancer-related deaths in men in the U.S. The development of chemotherapeutic agents that can bind PCa tumor cells with high specificity is critical in order to increase treatment effectiveness. Integrin receptors and their corresponding ligands have different expression patterns in PCa cells. They have been identified as promising targets to inhibit pathways involved in PCa progression. Currently, several compounds have proven to target specific integrins and their subunits in PCa cells. In this article, we review the role of integrins inhibitors in PCa and their potential as therapeutic targets for PCa treatments. We have discussed the following: natural compounds, monoclonal antibodies, statins, campothecins analog, aptamers, d-aminoacid, and snake venom. Recent studies have shown that their mechanisms of action result in decrease cell migration, cell invasion, cell proliferation, and metastasis of PCa cells.

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Abituzumab Targeting of αV-Class Integrins Inhibits Prostate Cancer Progression

Cited by 31 publications

References 26 publications

High αv Integrin Level of Cancer Cells Is Associated with Development of Brain Metastasis in Athymic Rats

High αv Integrin Level of Cancer Cells Is Associated with Development of Brain Metastasis in Athymic Rats

Translocating a High-Affinity Designer TIMP-1 to the Cell Membrane for Total Renal Carcinoma Inhibition: Putting the Prion Protein to Good Use

Integrin Inhibitors in Prostate Cancer

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