cholecystokinin and Glioblastoma

Glioblastoma multiforme (GBM) is the most malignant glioma. In the current study, 149 astrocytoma gene expression datasets were classified by prediction analysis of microarray. Strikingly, disks large homolog 3 (DLG3), a membrane-associated guanylate kinase-family gene, had the highest score in the GBM subset. DLG3 mRNA expression is significantly down-regulated in GBM relative to normal tissue and grade II or grade III astrocytoma according to the results of real-time polymerase chain reaction, and its protein expression shows an obvious difference by immunohistochemistry. Further assays show that DLG3 over-expression induces mitotic cell cycle arrest and apoptosis, and it inhibits proliferation and migration. However, DLG3 over-expression has almost no affect on invasion. The DLG3 protein expression in human brain GBM tissue and its effects on GBM cell invasion were not expected. Our data suggest that DLG3 is down-regulated in this cancer type. To our knowledge, this is the first report to clearly demonstrate the possible involvement of DLG3 in GBM.

Topics: Adult; Aged; Apoptosis; Brain; Brain Neoplasms; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Cholecystokinin; Down-Regulation; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Glioblastoma; Humans; Male; Middle Aged; Nuclear Proteins; Peptide Fragments; Retrospective Studies; Time Factors; Transcription Factors

The effects of gastrin (G17) on the growth and migration factors of four human melanoma cell lines (HT-144, C32, G-361, and SKMEL-28) were investigated. The expression patterns of cholecystokinin (CCK)(A), CCK(B), and CCK(C) gastrin receptors were investigated in these cells and in seven clinical samples by means of reverse transcription polymerase chain reaction. Melanoma cells appear to express mRNA for CCK(C) receptors, but not for CCK(A) or CCK(B) receptors. Although gastrin does not significantly modify the growth characteristics of the cell lines under study, it significantly modifies their cell migration characteristics. These modifications occur at adhesion level by modifying the expression levels of alpha(v) and beta3 integrins, at motility level by modifying the organization of the actin cytoskeleton, and at invasion level by modifying the expression levels of matrix metalloproteinase 14. We recently demonstrated the presence of CCK(B) receptors in mouse endothelial cells involved in glioblastoma neoangiogenesis. Chronic in vivo administration of a selective CCK(B) receptor antagonist to mice bearing xenografts of human C32 melanoma cells significantly decreased levels of neoangiogenesis, resulting in considerable delays in the growth of these C32 xenografts. In conclusion, our study identifies the pleiotropic effects of gastrin on melanoma cell biology.

Topics: Actins; Animals; Antineoplastic Agents; Apoptosis; Blotting, Western; Cell Line, Tumor; Cell Movement; Cholecystokinin; Cisplatin; Cytoskeleton; Dacarbazine; DNA Primers; DNA, Complementary; Flow Cytometry; Gastrins; Gene Expression Regulation, Neoplastic; Glioblastoma; Humans; Immunohistochemistry; Melanoma; Mice; Neoplasm Invasiveness; Neoplasm Transplantation; Neovascularization, Pathologic; Oligonucleotide Array Sequence Analysis; Poly(ADP-ribose) Polymerases; Receptor, Cholecystokinin B; Receptors, Cholecystokinin; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; RNA, Neoplasm; Time Factors; Wound Healing

Topics: Brain Neoplasms; Cholecystokinin; Glioblastoma; Humans; Receptors, Cholecystokinin

We have investigated the potential role of gastrin in the regulation of cell growth in human astrocytic tumors. To this end we have used synthetic analogs of gastrin and cholecystokinin (CCK) which behave as gastrin and/or CCK antagonists, e.g. compounds JMV-97, JMV-209 and JMV-179. Their effects on astrocytic tumor cell proliferation was investigated by the use of the colorimetric MTT assay. The in vitro biological models used in the present study included the SW1088, U87 and U373 astrocytic tumor cell lines. The results demonstrated marked influence of gastrin and CCK antagonists in the regulation of astrocytic tumor growth. This suggests that gastrin and/or CCK antagonists might be tested in experimental glioblastoma.

Topics: Astrocytes; Astrocytoma; Brain Neoplasms; Cholecystokinin; Gastrins; Glioblastoma; Humans; Peptide Fragments; Sincalide; Tumor Cells, Cultured