Involvement of caveolae and caveolae-like domains in signalling, cell survival and angiogenesis

Massimino, Maria Lina; Griffoni, Cristiana; Spisni, Enzo; Toni, Mattia; Tomasi, Vittorio

doi:10.1016/s0898-6568(01)00232-7

Cited by 72 publications

(52 citation statements)

References 65 publications

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“…According to a previous report, which investigated caveolin-1 (cav-1) in endothelial cells, PrP C is bound to cav-1 and, by recruiting Fyn kinase, can participate in signal transduction events related to cell survival, differentiation, and even angiogenesis (Massimino et al, 2002). In summary, taking our results in combination with these investigations (Massimino et al, 2002; Simak et A, primary cortical cultures were placed in a hypoxic chamber (95% N 2 and 5% CO 2 , 37°C) for 12 h and returned to a normoxic incubator (95% air and 5% CO 2 , 37°C) for different lengths of time (1, 3, 10, and 24 h), after which, total protein was extracted for Western blot analysis of PrP C . B, Densitometric analysis of the Western blot, the ratio of PrP C /actin was taken as 1 for nonhypoxic cells, which represents the control(C).ThemeanϮSEMisshown.…”

Section: Discussionmentioning

confidence: 78%

Overexpression of PrP^Cby Adenovirus-Mediated Gene Targeting Reduces Ischemic Injury in a Stroke Rat Model

Shyu¹,

Lin²,

Chiang³

et al. 2005

J. Neurosci.

116

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Prion diseases are induced by pathologically misfolded prion protein (PrPSc ), which recruit normal sialoglycoprotein PrP C by a templatedirected process. In this study, we investigated the expression of PrP C in a rat model of cerebral ischemia to more fully understand its physiological role. Immunohistochemical analysis demonstrated that PrP C -immunoreactive cells increased significantly in the penumbra of ischemic rat brain compared with the untreated brain. Western blot analysis showed that PrP C protein expression increased in ischemic brain tissue in a time-dependent manner. In addition, PrP C protein expression was seen to colocalize with neuron, glial, and vascular endothelial cells in the penumbric region of the ischemic brain. Overexpression of PrP C by injection of rAd (replication-defective recombinant adenoviral)-PGK (phosphoglycerate kinase)-PrP C -Flag into ischemic rat brain improved neurological behavior and reduced the volume of cerebral infarction, which is supportive of a role for PrP C in the neuroprotective adaptive cellular response to ischemic lesions. Concomitant upregulation of PrP C and activated extracellular signal-regulated kinase (ERK1/2) under hypoxia-reoxygenation in primary cortical cultures was shown to be dependent on ERK1/2 phosphorylation. During hypoxia-reoxygenation, mouse neuroblastoma cell line N18 cells transfected with luciferase rat PrP C promoter reporter constructs, containing the heat shock element (HSE), expressed higher luciferase activities (3-to 10-fold) than those cells transfected with constructs not containing HSE. We propose that HSTF-1 (hypoxia-activated transcription factor), phosphorylated by ERK1/2, may in turn interact with HSE in the promoter of PrP C resulting in gene expression of the prion gene. In summary, we conclude that upregulation of PrP C expression after cerebral ischemia and hypoxia exerts a neuroprotective effect on injured neural tissue. This study suggests that PrP C has physiological relevance to cerebral ischemic injury and could be useful as a therapeutic target for the treatment of cerebral ischemia.

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Section: Discussionmentioning

confidence: 78%

Overexpression of PrP^Cby Adenovirus-Mediated Gene Targeting Reduces Ischemic Injury in a Stroke Rat Model

Shyu¹,

Lin²,

Chiang³

et al. 2005

J. Neurosci.

116

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“…The growth and metastasis of prostate cancer and other tumors is dependent on the induction of new blood vessels from preexisting ones through angiogenesis (25,26). Cav-1 has been implicated in the regulation of endothelial cells proliferation, differentiation, and stabilization (6,17,27,28). In a study using Lewis lung carcinoma cells animal cancer model, cav-1 was found to be antiangiogenic factor (29).…”

Section: Discussionmentioning

confidence: 99%

Tumor Cell–Secreted Caveolin-1 Has Proangiogenic Activities in Prostate Cancer

Tahir¹,

Yang²,

Goltsov³

et al. 2008

Cancer Research

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Caveolin, a major structural component of specialized plasma membrane invaginations (caveolae) that participate in diverse cellular activities, has been implicated in the pathogenesis of several human diseases, including cancer. We showed in earlier studies that caveolin-1 (cav-1) is consistently and strongly overexpressed in metastatic prostate cancer and is secreted in a biologically active form by virulent prostate cancer cells. Using both in vitro and in vivo model systems, we now present evidence supporting a proangiogenic role for cav-1 in prostate cancer development and progression. Recombinant cav-1 (rcav-1) was taken up by cav-1 À/À endothelial cells through either a lipid raft/caveolae-or clathrin-dependent mechanism, leading to specific angiogenic activities (tubule formation, cell migration, and nitric oxide production) that were mediated by rcav-1 stimulation of the PI3K-Akt-eNOS signaling module. Pathologic angiogenesis induced by cav-1 in prostate cancer-bearing mice correlated with an increased frequency, number, and size of lung metastases. We propose that in addition to its antiapoptotic role, cav-1 secreted by prostate cancer cells functions critically as a proangiogenic factor in metastatic progression of this tumor. These new insights into cav-1 function in prostate cancer may provide a base for the design of clinically applicable therapeutic strategies. [Cancer Res 2008;68(3):731-9]

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“…Like other GPI-anchored proteins, PrP C has been localized to raft/caveolae-like membrane microdomains in most cell types, including neurons and cells of the immune system (Massimino et al, 2002). However, in contrast to the majority of GPIanchored proteins, which are sorted to the apical membrane of polarized cells, raft-associated PrP C was shown to be restricted to the basolateral membrane (Sarnataro et al, 2002) and/or intercellular junctions of polarized epithelial cells (Morel et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Junctional expression of the prion protein PrPC by brain endothelial cells: a role in trans-endothelial migration of human monocytes

Viegas

Chaverot

Enslen

et al. 2006

Journal of Cell Science

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The conversion of prion protein (PrPC) to its protease-resistant isoform is involved in the pathogenesis of prion diseases. Although PrPC is highly expressed in neurons and other cell types, its physiological function still remains elusive. Here, we describe how we evaluated its expression, subcellular localization and putative function in brain endothelial cells, which constitute the blood-brain barrier. We detected its expression in microvascular endothelium in mouse brain sections and at intercellular junctions of freshly isolated brain microvessels and cultured brain endothelial cells of mouse, rat and human origin. PrPC co-localized with the adhesion molecule platelet endothelial cell adhesion molecule-1 (PECAM-1); moreover, both PrPC and PECAM-1 were present in raft membrane microdomains. Using mixed cultures of wild-type and PrPC-deficient mouse brain endothelial cells, we observed that PrPC accumulation at cell-cell contacts was probably dependent on homophilic interactions between adjacent cells. Moreover, we report that anti-PrPC antibodies unexpectedly inhibited transmigration of U937 human monocytic cells as well as freshly isolated monocytes through human brain endothelial cells. Significant inhibition was observed with various anti-PrPC antibodies or blocking anti-PECAM-1 antibodies as control. Our results strongly support the conclusion that PrPC is expressed by brain endothelium as a junctional protein that is involved in the trans-endothelial migration of monocytes.

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Involvement of caveolae and caveolae-like domains in signalling, cell survival and angiogenesis

Cited by 72 publications

References 65 publications

Overexpression of PrP^Cby Adenovirus-Mediated Gene Targeting Reduces Ischemic Injury in a Stroke Rat Model

Overexpression of PrP^Cby Adenovirus-Mediated Gene Targeting Reduces Ischemic Injury in a Stroke Rat Model

Tumor Cell–Secreted Caveolin-1 Has Proangiogenic Activities in Prostate Cancer

Junctional expression of the prion protein PrPC by brain endothelial cells: a role in trans-endothelial migration of human monocytes

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Involvement of caveolae and caveolae-like domains in signalling, cell survival and angiogenesis

Cited by 72 publications

References 65 publications

Overexpression of PrPCby Adenovirus-Mediated Gene Targeting Reduces Ischemic Injury in a Stroke Rat Model

Overexpression of PrPCby Adenovirus-Mediated Gene Targeting Reduces Ischemic Injury in a Stroke Rat Model

Tumor Cell–Secreted Caveolin-1 Has Proangiogenic Activities in Prostate Cancer

Junctional expression of the prion protein PrPC by brain endothelial cells: a role in trans-endothelial migration of human monocytes

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Overexpression of PrP^Cby Adenovirus-Mediated Gene Targeting Reduces Ischemic Injury in a Stroke Rat Model

Overexpression of PrP^Cby Adenovirus-Mediated Gene Targeting Reduces Ischemic Injury in a Stroke Rat Model