Direct contact with perivascular tumor cells enhances integrin αvβ3 signaling and migration of endothelial cells

Burgett, Monica E.; Lathia, Justin D.; Roth, Patrick; Nowacki, Amy S.; Galileo, Deni S.; Pugacheva, Elena N.; Huang, Ping; Vasanji, Amit; Li, Meizhang; Byzova, Tatiana V.; Mikkelsen, Tom; Bao, Shideng; Rich, Jeremy; Gladson, Candece L.

doi:10.18632/oncotarget.9700

Cited by 30 publications

(29 citation statements)

References 62 publications

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“…In addition, complex molecular signaling and crosstalk between glioma cells and the cells of the NVU also dictate tumor survival and progression (71)(72)(73)(74). These cell-cell interactions promote tumorigenic processes and disrupt normal NVU functions.…”

Section: Neoplastic Diseasementioning

confidence: 99%

The Translational Significance of the Neurovascular Unit

McConnell

Kersch

Woltjer

et al. 2017

Journal of Biological Chemistry

258

194

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Edited by Paul E. FraserThe mammalian brain is supplied with blood by specialized vasculature that is structurally and functionally distinct from that of the periphery. A defining feature of this vasculature is a physical blood-brain barrier (BBB). The BBB separates blood components from the brain microenvironment, regulating the entry and exit of ions, nutrients, macromolecules, and energy metabolites. Over the last two decades, physiological studies of cerebral blood flow dynamics have demonstrated that substantial intercellular communication occurs between cells of the vasculature and the neurons and glia that abut the vasculature. These findings suggest that the BBB does not function independently, but as a module within the greater context of a multicellular neurovascular unit (NVU) that includes neurons, astrocytes, pericytes, and microglia as well as the blood vessels themselves. Here, we describe the roles of these NVU components as well as how they act in concert to modify cerebrovascular function and permeability in health and in select diseases.

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Section: Neoplastic Diseasementioning

confidence: 99%

The Translational Significance of the Neurovascular Unit

McConnell

Kersch

Woltjer

et al. 2017

Journal of Biological Chemistry

258

194

View full text Add to dashboard Cite

show abstract

“…Regarding PI3K/Akt, a recent study associates this pathway with Plexin-B1/Rho/αvβ3 and Serine/arginine Protein Kinase-1 [ 79 ]. Moreover, migration can be improved by αvβ3 interaction with pleiotrophin (a secreted heparin-binding cytokine) on GB cells and EC [ 80 ] and with the cell adhesion molecule L1CAM on GIC [ 81 ]. Besides αvβ3/αvβ5, β1 is also involved in GB angiogenesis [ 76 ].…”

Section: Roles Of Integrins In Glioblastomamentioning

confidence: 99%

Interest of integrins targeting in glioblastoma according to tumor heterogeneity and cancer stem cell paradigm: an update

et al. 2017

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Glioblastomas are malignant brain tumors with dismal prognosis despite standard treatment with surgery and radio/chemotherapy. These tumors are defined by an important cellular heterogeneity and notably contain a particular subpopulation of Glioblastoma-initiating cells, which recapitulate the heterogeneity of the original Glioblastoma. In order to classify these heterogeneous tumors, genomic profiling has also been undertaken to classify these heterogeneous tumors into several subtypes. Current research focuses on developing therapies, which could take into account this cellular and genomic heterogeneity. Among these targets, integrins are the subject of numerous studies since these extracellular matrix transmembrane receptors notably controls tumor invasion and progression. Moreover, some of these integrins are considered as membrane markers for the Glioblastoma-initiating cells subpopulation. We reviewed here integrin expression according to glioblastoma molecular subtypes and cell heterogeneity. We discussed their roles in glioblastoma invasion, angiogenesis, therapeutic resistance, stemness and microenvironment modulations, and provide an overview of clinical trials investigating integrins in glioblastomas. This review highlights that specific integrins could be identified as selective glioblastoma cells markers and that their targeting represents new diagnostic and/or therapeutic strategies.

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“…The expression of L1CAM by various types of cancer cells is utilized to engage αVβ3 on endothelial cells. It has been demonstrated that L1CAM expression in glioma tumor cells serves to promote the motility of both cancer cells [ 31 ] and endothelial cells [ 32 ], thus having important implications for both metastasis and angiogenesis, respectively. Other non-ECM integrin ligands have been implicated in tumor cell migration.…”

Section: Integrin-mediated Cell-cell Interactionsmentioning

confidence: 99%

Beyond the Matrix: The Many Non-ECM Ligands for Integrins

LaFoya

Munroe

Miyamoto

et al. 2018

IJMS

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The traditional view of integrins portrays these highly conserved cell surface receptors as mediators of cellular attachment to the extracellular matrix (ECM), and to a lesser degree, as coordinators of leukocyte adhesion to the endothelium. These canonical activities are indispensable; however, there is also a wide variety of integrin functions mediated by non-ECM ligands that transcend the traditional roles of integrins. Some of these unorthodox roles involve cell-cell interactions and are engaged to support immune functions such as leukocyte transmigration, recognition of opsonization factors, and stimulation of neutrophil extracellular traps. Other cell-cell interactions mediated by integrins include hematopoietic stem cell and tumor cell homing to target tissues. Integrins also serve as cell-surface receptors for various growth factors, hormones, and small molecules. Interestingly, integrins have also been exploited by a wide variety of organisms including viruses and bacteria to support infectious activities such as cellular adhesion and/or cellular internalization. Additionally, the disruption of integrin function through the use of soluble integrin ligands is a common strategy adopted by several parasites in order to inhibit blood clotting during hematophagy, or by venomous snakes to kill prey. In this review, we strive to go beyond the matrix and summarize non-ECM ligands that interact with integrins in order to highlight these non-traditional functions of integrins.

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Direct contact with perivascular tumor cells enhances integrin αvβ3 signaling and migration of endothelial cells

Cited by 30 publications

References 62 publications

The Translational Significance of the Neurovascular Unit

The Translational Significance of the Neurovascular Unit

Interest of integrins targeting in glioblastoma according to tumor heterogeneity and cancer stem cell paradigm: an update

Beyond the Matrix: The Many Non-ECM Ligands for Integrins

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