Epidermal growth factor differentially regulates low density lipoprotein receptor-related protein gene expression in neoplastic and fetal human astrocytes

Hussaini, Isa M.; Brown, Morry D.; Karns, Larry R.; Carpenter, Joan E.; Redpath, Gerald T.; Gonias, Steven L.

doi:10.1002/(sici)1098-1136(19990101)25:1<71::aid-glia7>3.0.co;2-0

Cited by 21 publications

(9 citation statements)

References 69 publications

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“…The specificity of the induced antibody response was examined in U251MG glioblastoma cells, which has a high expression of the a-macroglobulin receptor (Hussaini et al, 1999), which is the receptor protein to which the PE binds. Serum from IT-treated immunocompetent animals was analysed for the presence of neutralising anti-IT-antibodies on PE-induced cytotoxicity in the MTS assay ( Figure 5B) and on PE-induced inhibition of protein synthesis ( 3 H-leucine incorporation assay) ( Figure 5C).…”

Section: Csa Prevented Antibody Immune Response Against It In Vivomentioning

confidence: 99%

Synergistic anti-cancer effects of immunotoxin and cyclosporin in vitro and in vivo

2009

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BACKGROUND: The clinical use of immunotoxins (ITs) has been hampered by hepatotoxicity, and the induction of a strong human-anti-IT response. The human-anti-IT response results in neutralisation of the immunoconjugates, rendering repetitive treatment inefficacious. METHODS: We evaluated the combination of cyclosporin A (CsA) with various Pseudomonas exotoxin A-based ITs in human breast, cervical, and prostate cancer cell lines measured by protein synthesis, cell viability, and TUNEL assay. Furthermore, expression of essential proteins were analysed by western blot. We used cervical cancer model in nude rats to evaluate the anti-metastatic effect of the combination. The anti-immunogenic response by the CsA treatment was investigated in immunocompetent rats. RESULTS: The combination of CsA with ITs caused remarkable synergistic cytotoxicity, in several cancer cell lines, characterised by protein synthesis inhibition, decreased cell viability, and an increased apoptotic index. Furthermore, the combination strongly inhibited formation of metastases in a cervical cancer model in nude rats with a statistically significant increase in median survival time of the combination-treated animals, as compared with those receiving a suboptimal dose of IT alone. Notably, we found in immunocompetent rats that the anti-IT immunoresponse elicited by repeated administration of IT was efficiently abrogated by CsA; notably the antibody responds towards the highly immunogenic PE was shown to be prevented. CONCLUSION: The combination of ITs and CsA might constitute a significant improvement in the clinical potential of systemic IT treatment of cancer patients.

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Section: Csa Prevented Antibody Immune Response Against It In Vivomentioning

confidence: 99%

Synergistic anti-cancer effects of immunotoxin and cyclosporin in vitro and in vivo

2009

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“…Western blot analysis was done as previously described (33). Briefly, cell cultures were extracted with 1% Triton X-100, 50 mmol/L Tris (pH 7.5), and 150 nmol/L NaCl in the presence of 2 mmol/L EDTA, 100 Amol/L phenylmethylsulfonyl fluoride, 5 Ag/mL leupeptin, and 1 Ag/mL aprotinin.…”

Section: Western Blot Analysismentioning

confidence: 99%

“…These constructs and LRPdeficient clones were previously reported (33). For uPA antisense, uPA cDNA served as the starting template.…”

Section: Stable Expression Of Lrp and Upa Antisense In Glioblastoma Cmentioning

confidence: 99%

Protein Kinase C-α–Mediated Regulation of Low-Density Lipoprotein Receptor–Related Protein and Urokinase Increases Astrocytoma Invasion

Amos

Mut²,

diPierro

et al. 2007

Cancer Research

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Aggressive and infiltrative invasion is one of the hallmarks of glioblastoma. Low-density lipoprotein receptor-related protein (LRP) is expressed by glioblastoma, but the role of this receptor in astrocytic tumor invasion remains poorly understood. We show that activation of protein kinase C-A (PKC-A) phosphorylated and down-regulated LRP expression. Pretreatment of tumor cells with PKC inhibitors, phosphoinositide 3-kinase (PI3K) inhibitor, PKC-A small interfering RNA (siRNA), and short hairpin RNA abrogated phorbol 12-myristate 13-acetate-induced down-regulation of LRP and inhibited astrocytic tumor invasion in vitro. In xenograft glioblastoma mouse model and in vitro transmembrane invasion assay, LRPdeficient cells, which secreted high levels of urokinase-type plasminogen activator (uPA), invaded extensively the surrounding normal brain tissue, whereas the LRP-overexpressing and uPA-deficient cells did not invade into the surrounding normal brain. siRNA, targeted against uPA in LRP-deficient clones, attenuated their invasive potential. Taken together, our results strongly suggest the involvement of PKC-A/PI3K signaling pathways in the regulation of LRP-mediated astrocytoma invasion. Thus, a strategy of combining small molecule inhibitors of PKC-A and PI3K could provide a new treatment paradigm for glioblastomas. [Cancer Res 2007;67(21):10241-51]

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“…Both cell lines were isolated from human glioblastomas and various characteristics have been described (Bigner et al, 1981;Bongcam-Rudloff et al, 1991;Uhrbom et al, 1997;Hussaini et al, 1999). U-1242-Z cells are U-1242 cells that stably express PKC-Z (Hussaini et al, 2000).…”

Section: Cell Culturesmentioning

confidence: 99%

“…3 H-thymidine incorporation Briefly, as reported previously (Hussaini et al, 1999), cells were treated with PMA (100 nM) for 20 h, washed with calciumand magnesium-free PBS and subsequently pulsed with 3 H-thymidine (2 mCi/ml for 2 h at 371C). Cells were lysed in 1 N NaOH.…”

Section: Cell Culturesmentioning

confidence: 99%

The protein kinase C-η isoform induces proliferation in glioblastoma cell lines through an ERK/Elk-1 pathway

et al. 2006

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Epidermal growth factor differentially regulates low density lipoprotein receptor-related protein gene expression in neoplastic and fetal human astrocytes

Cited by 21 publications

References 69 publications

Synergistic anti-cancer effects of immunotoxin and cyclosporin in vitro and in vivo

Synergistic anti-cancer effects of immunotoxin and cyclosporin in vitro and in vivo

Protein Kinase C-α–Mediated Regulation of Low-Density Lipoprotein Receptor–Related Protein and Urokinase Increases Astrocytoma Invasion

The protein kinase C-η isoform induces proliferation in glioblastoma cell lines through an ERK/Elk-1 pathway

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