Caveolin‐1 expression is maintained in rat and human astroglioma cell lines

Cameron, Patricia L.; Liu, Changdan; Smart, Dee Dee; Hantus, Stephen; Fick, James; Cameron, Richard S.

doi:10.1002/glia.10036

Cited by 32 publications

(39 citation statements)

References 57 publications

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“…The endocytosis of receptorligand complexes is generally because of dynamin-mediated endocytosis via clathrin coated pits (39). However, caveolin-1 expression has been demonstrated in several rat and human astroglioma cell lines (40) and the entry of certain pathogens and toxins into host cells has also been shown to occur via caveolae (53)(54)(55). Indeed, the internalization of cholera toxin into CACO-2 cells can be inhibited by filipin (39) a finding that is consistent with our findings on Cltx.…”

Section: Discussionmentioning

confidence: 99%

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Chlorotoxin Inhibits Glioma Cell Invasion via Matrix Metalloproteinase-2

Deshane

Garner

Sontheimer

2003

Journal of Biological Chemistry

355

331

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Primary brain tumors (gliomas) have the unusual ability to diffusely infiltrate the normal brain thereby evading surgical treatment. Chlorotoxin is a scorpion toxin that specifically binds to the surface of glioma cells and impairs their ability to invade. Using a recombinant His-Cltx we isolated and identified the principal Cltx receptor on the surface of glioma cells as matrix metalloproteinase-2 (MMP-2). MMP-2 is specifically upregulated in gliomas and related cancers, but is not normally expressed in brain. We demonstrate that Cltx specifically and selectively interacts with MMP-2 isoforms, but not with MMP-1, -3, and -9, which are also expressed in malignant glioma cells. Importantly, we show that the anti-invasive effect of Cltx on glioma cells can be explained by its interactions with MMP-2. Cltx exerts a dual effect on MMP-2: it inhibits the enzymatic activity of MMP-2 and causes a reduction in the surface expression of MMP-2. These findings suggest that Cltx is a specific MMP-2 inhibitor with significant therapeutic potential for gliomas and other diseases that invoke the activity of MMP-2.

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Section: Discussionmentioning

confidence: 99%

“…Receptor-mediated endocytosis has been shown to occur either by a clathrin-mediated pathway (39) or by caveoli (40). To assess whether this observed MMP-2 internalization by Cltx is via caveolae, we examined cell surface expression of MMP-2 in the presence and absence of filipin, a sterol binding drug known to disrupt caveolae (41).…”

Section: Figmentioning

confidence: 99%

Chlorotoxin Inhibits Glioma Cell Invasion via Matrix Metalloproteinase-2

Deshane

Garner

Sontheimer

2003

Journal of Biological Chemistry

355

331

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“…However, increased expression of caveolin-1 has also been associated with development of various tumors including prostate and breast cancers (Thompson, 1998;Yang et al, 1998;Kato et al, 2002). A recent study (Cameron et al, 2002) reported that the caveolin-1 mRNA and protein were expressed at variable levels in Figure 7 Effects of EGFR or EGFRvIII tyrosine phosphorylation on their interactions with caveolin-1 determined by immunocytochemistry. (a-f) Caveolin-1 (red fluorescence) and EGFR (green fluorescence) immunostaining in control U87MG cells (a-c) and cells subjected to 100 ng/ml EGF for 10 min (d-f) and their colocalization (c, f).…”

Section: Discussionmentioning

confidence: 99%

Interactions of EGFR and caveolin-1 in human glioblastoma cells: evidence that tyrosine phosphorylation regulates EGFR association with caveolae

et al. 2004

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Epidermal growth factor receptor (EGFR) amplification and type III mutation (EGFRvIII), associated with constitutive tyrosine kinase activation and high malignancy, are commonly observed in glioblastoma tumors. The association of EGFR and EGFRvIII with caveolins was investigated in human glioblastoma cell lines, U87MG and U87MG-EGFRvIII. Caveolin-1 expression, determined by RT-PCR, real-time quantitative PCR and Western blot, was upregulated in glioblastoma cell lines (two-fold) and tumors (20-300-fold) compared to primary human astrocytes and nonmalignant brain tissue, respectively. U87MG-EGFRvIII expressed higher levels of caveolin-1 than U87MG. In contrast, the expression of caveolin-2 and -3 were downregulated in glioblastoma cells compared to astrocytes. A colocalization of EGFR, but not of EGFRvIII, with lipid rafts and caveolin-1 was observed by immunocytochemistry. Association of EGFR and EGFRvIII with caveolae, assessed in vitro by binding to caveolin scaffolding domain peptides and in vivo by immunocolocalization studies in cells and caveolae-enriched cellular fraction, was phosphorylation-dependent: ligand-induced phosphorylation of EGFR resulted in dissociation of EGFR from caveolae. In contrast, inhibition of the EGFRvIII constitutive tyrosine phosphorylation by AG1478 increased association of EGFRvIII with caveolin-1. AG1478 also increased caveolin-1 expression and reduced glioblastoma cell growth in a semi-solid agar. The evidence suggests that the phosphorylation-regulated sequestration of EGFR in caveolae may be involved in arresting constitutive or ligand-induced signaling through EGFR responsible for glial cell transformation.

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“…In astrocytes, clathrin-independent caveolar endocytosis has been reported previously (Cameron et al, 2002). To investigate whether the constitutive endocytosis in astrocytes is caveolin dependent, we performed live FM staining of astrocytes followed by retrospective immunostaining with caveolin-1, which specifically labels caveolar structures (Fig.…”

Section: Astroglial Constitutive Endocytosis Is Caveolin Independentmentioning

confidence: 92%

Ca2+ Regulation of Dynamin-Independent Endocytosis in Cortical Astrocytes

Jiang

Chen

2009

Journal of Neuroscience

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Astrocytes release ATP and glutamate through vesicular exocytosis to mediate neuron-glial interactions. In contrast to exocytosis, the endocytic pathways in astroglial cells are poorly understood. Here, we identify a constitutive endocytic pathway in cultured astrocytes that is dependent on neither clathrin nor dynamin. This dynamin-independent endocytic pathway is regulated by Rab5, an early endosome protein. The endocytosed vesicles show fast transition from early endosomes to late endosomes and lysosomes within a few minutes. Interestingly, this clathrin-and dynamin-independent endocytosis in astrocytes is potently regulated by intracellular Ca 2ϩ . ATP and glutamate greatly enhance the dynamin-independent endocytosis through elevating the intracellular Ca 2ϩ . In addition, amyloid-␤ peptide (A␤) also enhances the dynamin-independent endocytosis by inducing Ca 2ϩ transients in astrocytes. These results demonstrate a novel endocytic pathway in glial cells that is dynamin independent but tightly regulated by intracellular Ca 2ϩ . The regulation by ATP, glutamate, and A␤ suggests an important role of the dynamin-independent endocytosis in both physiological and pathological conditions.

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Caveolin‐1 expression is maintained in rat and human astroglioma cell lines

Cited by 32 publications

References 57 publications

Chlorotoxin Inhibits Glioma Cell Invasion via Matrix Metalloproteinase-2

Chlorotoxin Inhibits Glioma Cell Invasion via Matrix Metalloproteinase-2

Interactions of EGFR and caveolin-1 in human glioblastoma cells: evidence that tyrosine phosphorylation regulates EGFR association with caveolae

Ca2+ Regulation of Dynamin-Independent Endocytosis in Cortical Astrocytes

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