Gastrin inhibits motility, decreases cell death levels and increases proliferation in human glioblastoma cell lines

Hauwer, Christophe De; Camby, Isabelle; Darro, Francis; Migeotte, Isabelle; Decaestecker, Christine; Verbeek, Claude; Danguy, André; Pasteels, Jean-Lambert; Brotchi, Jacques; Salmon, Isabelle; Ham, Philippe Van; Kiss, Róbert

doi:10.1002/(sici)1097-4695(19981115)37:3<373::aid-neu3>3.0.co;2-h

Cited by 52 publications

(46 citation statements)

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“…Since we had observed that gastrin is able to signi®cantly modulate the migration of human glioblastoma cells (DeHauwer et al, 1998), in our present study we have investigated some of the molecular mechanisms by which gastrin could modulate this glioblastoma cell motility. We chose the U373 human glioblastoma cell line as an experimental model because we have already shown that close biological similarities exist between this experimental glioblastoma and highgrade human astrocytic tumors obtained directly from surgical resections (Kruczynski et al, 1995;Camby et al, 2001).…”

Section: Discussionmentioning

confidence: 98%

“…Gastrin-related peptides (like cholecystokinin, CCK) constitute the most abundant peptide system in the brain and, vice versa, the brain is the main CCK production site (Rehfeld and Van Solidge, 1991). We have already shown that gastrin is able to modify not only the cell proliferation level in human glioblastomas (Camby et al, 1994(Camby et al, , 1996, but also their level of migration (DeHauwer et al, 1998). De la Fuente's group has also evidenced the e ect of gastrin on the migration features of various cells of the immune system (De la Fuente et al, 1997Fuente et al, , 1998.…”

Section: Introductionmentioning

confidence: 96%

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Gastrin induces over-expression of genes involved in human U373 glioblastoma cell migration

et al. 2001

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Astrocytic tumors are the most common and the most malignant primary tumors of the central nervous system. We had previously observed that gastrin could signi®-cantly modulate both cell proliferation and migration of astrocytoma cells. We have investigated in the present study which genes could be targeted by gastrin in tumor astrocyte migration. Using a subtractive hybridization PCR technique we have cloned genes di erentially overexpressed in human astrocytoma U373 cells treated or not with gastrin. We found about 70 genes overexpressed by gastrin. Among the genes overexpressed by gastrin, we paid particular attention to tenascin-C, S100A6 and MLCK genes because their direct involvement in cell migration features. Their gastrin-induced overexpression was quantitatively determined by competitive RT ± PCR technique. We also showed by means of a reporter gene system that S100A6 and tenascin-C respective promoters were upregulated after gastrin treatment. These data show that gastrin-mediated e ects in glioblastoma cells occur through activation of a number of genes involved in cell migration and suggest that gastrin could be a target in new therapeutic strategies against malignant gliomas. Oncogene (2001) 20, 7021 ± 7028.

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 96%

Gastrin induces over-expression of genes involved in human U373 glioblastoma cell migration

et al. 2001

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“…The in vitro anti-cancer effects of ISP at its IC 50 concentration (PC-3 cancer cells) or at 5-fold its IC 50 concentration (U373 and A549 cancer cells) were visualized by means of computer-assisted phase-contrast microscopy, i.e., quantitative videomicroscopy (20,21). Cells were monitored for 72 h. 'Movies' were built on the obtained time-lapse image sequences and enabled a rapid screening for cell viability (20,21).…”

Section: In Vitro Computer-assisted Phase-contrast Microscopy Analysementioning

confidence: 99%

“…Cells were monitored for 72 h. 'Movies' were built on the obtained time-lapse image sequences and enabled a rapid screening for cell viability (20,21). In each control or ISP-treated condition, the cell growth level was evaluated by the ratio between the numbers of cells counted in the last and first frames of the image sequences (21,22).…”

Section: In Vitro Computer-assisted Phase-contrast Microscopy Analysementioning

confidence: 99%

Isostrychnopentamine, an indolomonoterpenic alkaloid from Strychnos usambarensis, with potential anti-tumor activity against apoptosis-resistant cancer cells

Baldé

Mégalizzi²,

Cao³

et al. 2010

Int J Oncol

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Abstract. Isostrychnopentamine (ISP) is an indolomonoterpenic alkaloid that is present in the leaves of Strychnos usambarensis, an East African small tree. We have reported previously pro-apoptotic effects induced in vitro by ISP in the human HCT-116 colon cancer cell line, a model that displays relative sensitivity to apoptosis. In the present study, we observed that the in vitro growth inhibitory activities of ISP are similar in cancer cells that display sensitivity versus resistance to apoptosis. We made use of the U373 glioblastoma and the A549 non-small cell lung cancer (NSCLC) cell lines as models relatively resistant to apoptosis, and the human PC-3 prostate cancer cell line as a model relatively sensitive to apoptosis. While ISP induced transient decreases in [ATP] i and apoptosis in human U373 GBM cells, it did not provoke such features in A549 NSCLC cells. It thus seems that ISPinduced anti-cancer activity can lead to pro-apoptotic effects as a consequence, while apoptosis seems not to be the main cause by which ISP induces cancer cell death. ISP is a compound that merits further investigations in order to: i) identify the mechanism(s) of action by which it kills cancer cells, and ii) hemisynthesize novel ISP derivatives aiming to overcome, at least partly, the resistance of metastatic cancers to apoptosis. IntroductionDespite frequent responses to chemotherapy, curative treatment remains elusive for the majority of patients with metastatic solid tumors (1). Indeed, in the common advanced cancers, over 40 years of cytotoxic drug development has brought no significant change in cure rates (1). Savage and colleagues (1) report that one interpretation is that the intrinsic properties of the malignancies themselves, rather than the qualities of individual drugs or combination therapies, are primarily responsible for their curability with chemotherapy. These authors thus suggest that the curability of these malignancies results from an intrinsic 'locked-in' state of sensitivity to proapoptotic stresses in these cells (1). In fact, >90% of cancer patients die from their metastases (2). Drug resistance, either acquired or intrinsic, often prevents tumor cells from undergoing sufficient levels of apoptosis, resulting in cancer cell survival and treatment failure (1,2). The metastatic process is inherent to a significant level of resistance to apoptosis. Indeed, as a barrier to metastases, cells normally undergo apoptosis after they lose contact with their extra cellular matrix or their neighboring cells (3). This cell death process has been termed 'anoikis' (3). Tumor cells that acquire malignant potential have developed mechanisms to resist anoikis and thereby survive after detachment from their primary site and while travelling through the lymphatic and circulatory systems (3). Defects in the death receptor pathway of caspase activation, such as the over-expression of the caspase-8 inhibitor FLIP, can render cells resistant to anoïkis (3).Plants have played a dominant role in the development of sophisticate...

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“…28 In addition, gastrin has been shown to modulate cell death in the glioblastoma cell lines U373MG and U87MG when added to the medium. 39 The level of active gastrin may, therefore, be one effector, by which SGNE1/7B2 expression influences the tumorbiological properties of glioblastoma cells. Furin, another member of the Ca 2þ -dependent serine endoprotease family is overexpressed in the glioblastoma cell lines U87MG and U118MG.…”

Section: Discussionmentioning

confidence: 99%

Frequent epigenetic inactivation of the chaperone SGNE1/7B2 in human gliomas

Waha

Felsberg

Hartmann

et al. 2011

Intl Journal of Cancer

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In a genome-wide screen using DMH (differential methylation hybridization) we have identified a CpG island within the 5 0 region and untranslated first exon of the secretory granule neuroendocrine protein 1 gene (SGNE1/7B2) that showed hypermethylation in low-and high-grade astrocytomas compared to normal brain tissue. Pyrosequencing was performed to confirm the methylation status of this CpG island in 89 astrocytic gliomas of different malignancy grades and six glioma cell lines. Hypermethylation of SGNE1/7B2 was significantly more frequent in diffuse low-grade astrocytomas as well as secondary glioblastomas and anaplastic astrocytomas as compared to primary glioblastomas. mRNA expression analysis by real-time RT-PCR indicates that SGNE1/7B2 expression is downregulated in astrocytic gliomas compared to white matter samples. Treatment of glioma cells with the demethylating agent 5-aza-2 0 -deoxycytidine restores the transcription of SGNE1/7B2. Overexpression of SGNE1/7B2 in T98G, A172 and U373MG glioblastoma cells significantly suppressed focus formation and led to a significant increase in apoptotic cells as determined by flow cytometric analysis in T98G cells. In summary, we have identified SGNE1/7B2 as a novel target silenced by DNA methylation in astrocytic gliomas. The high incidence of this alteration and the significant effects of SGNE1/7B2 on the growth and apoptosis of glioblastoma cells provide a first proof for a functional implication of SGNE1/7B2 inactivation in the molecular pathology of gliomas.Glioblastomas are the most frequent and most malignant tumors arising in the brain with a peak incidence between 45 and 70 years. 1 Despite recent therapeutic advances, these tumors respond poorly to radiation therapy and most forms of chemotherapy and retain a dismal prognosis with most patients dying within 1 year after diagnosis. Glioblastomas WHO Grade IV may develop through malignant progression from diffuse astrocytomas WHO Grade II or anaplastic astrocytomas WHO Grade III (secondary glioblastoma), but more frequently, de novo without evidence of a less malignant precursor lesion (primary glioblastoma). Several comprehensive profiling studies have uncovered a high incidence of genetic and epigenetic alterations in glioblastomas, some of which are specific for certain clinical glioblastoma subtypes. Primary glioblastomas frequently show loss of heterozygosity on chromosome 10q (70% of cases), EGFR amplification (36%), p16 (INK4a) deletion (31%) and PTEN mutations (25%). 2 Secondary glioblastomas as well as their lower grade precursor lesions exhibit frequent mutations of the TP53 and IDH1 genes. 2,3 Loss of genetic material from chromosome 10q25-qter is associated with both primary and secondary glioblastomas. 2 Promoter CpG island hypermethylation generally results in transcriptional silencing of associated genes and is crucial for the development of cancer. 4 Epigenetic alterations within promoter regions effect the binding affinity of transcription factors by interfering with transcription initiatio...

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Gastrin inhibits motility, decreases cell death levels and increases proliferation in human glioblastoma cell lines

Cited by 52 publications

References 59 publications

Gastrin induces over-expression of genes involved in human U373 glioblastoma cell migration

Gastrin induces over-expression of genes involved in human U373 glioblastoma cell migration

Isostrychnopentamine, an indolomonoterpenic alkaloid from Strychnos usambarensis, with potential anti-tumor activity against apoptosis-resistant cancer cells

Frequent epigenetic inactivation of the chaperone SGNE1/7B2 in human gliomas

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