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Role fibroblastového aktivačního proteinu v růstu a invazivitě gliomových buněk
Fejfarová, Edita ; Bušek, Petr (advisor) ; Szabo, Pavol (referee)
High grade astrocytomas are very progressive brain tumors. Glioblastoma multiforme is the most frequent and the most malignant type with very infiltrative phenotype of the tumor cells. Fibroblast activation protein FAP is a predominantly membrane bound prolyl peptidase bearing exo- and endopeptidase hydrolytic activities. FAP is known to play a role in wound healing, cell migration and invasion and its expression is linked to the pathogenesis of several malignancies. mRNA expression of FAP is upregulated in 48% of glioblastomas according to The Cancer Genome Atlas microarray data. The involvement of FAP in the pathogenesis of astrocytic tumors is largely unknown. The aims of this work are to analyse the expression of FAP in primary cell cultures derived from high grade gliomas and to analyse the influence of FAP on the growth, migration and invasion of glioma cells. Our ELISA and western blot results showed heterogenous expression of FAP in the studied glioma primary cell cultures and cell lines. Both enzymatic activities characteristic of FAP were detected in the primary glioma cell culture P11 with high expression of FAP. In these cells, FAP was present not only in the typical plasma membrane localization, but also in the cytoplasm as demonstrated by immunofluorescence staining. The P11 cells...
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The role of dipeptidyl peptidase-IV and homologous proteases in migration and invasion.
Fejfarová, Edita ; Bušek, Petr (advisor) ; Rösel, Daniel (referee)
Migration and invasion are processes which naturally occur in organism during embryogenesis, immune reactions or wound healing. These processes are very important factors in some serious diseases like rheumatoid arthritis and carcinogenesis. There is no doubt about contribution of proteases in these processes-many of them degrade extracellular matrix and thereby facilitate the movement of cells. While dipeptidylpeptidase-IV cleaves solely two amino acids from N-terminus so it is not considerably involved in ECM degradation. DPPIV and its homologues recognize peptides with proline on penultimate position, which causes resistance to ordinary types of proteases. Substrates of DPPIV and its activity homologues include chemokines implicated in signalling of migration - their cleavage and thus inactivation present DPPIV and DPPIV-like molecules as modulators of cell migration signalling in choriocacinoma, neuroblastoma, on Sézary cells or epithelial cells migrating in response to injury. Another activity of some DPPIV-like proteases is binding to the extracellular matrix proteins, when are helping in the attachment of cells and thus affect the migratory ability of the cells like ovarian cancer cells, prostate cancer cells, melanoma cells or kidney cells. Effects on migration and invasion have also...
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Role fibroblastového aktivačního proteinu v růstu a invazivitě gliomových buněk
Fejfarová, Edita ; Bušek, Petr (advisor) ; Szabo, Pavol (referee)
High grade astrocytomas are very progressive brain tumors. Glioblastoma multiforme is the most frequent and the most malignant type with very infiltrative phenotype of the tumor cells. Fibroblast activation protein FAP is a predominantly membrane bound prolyl peptidase bearing exo- and endopeptidase hydrolytic activities. FAP is known to play a role in wound healing, cell migration and invasion and its expression is linked to the pathogenesis of several malignancies. mRNA expression of FAP is upregulated in 48% of glioblastomas according to The Cancer Genome Atlas microarray data. The involvement of FAP in the pathogenesis of astrocytic tumors is largely unknown. The aims of this work are to analyse the expression of FAP in primary cell cultures derived from high grade gliomas and to analyse the influence of FAP on the growth, migration and invasion of glioma cells. Our ELISA and western blot results showed heterogenous expression of FAP in the studied glioma primary cell cultures and cell lines. Both enzymatic activities characteristic of FAP were detected in the primary glioma cell culture P11 with high expression of FAP. In these cells, FAP was present not only in the typical plasma membrane localization, but also in the cytoplasm as demonstrated by immunofluorescence staining. The P11 cells...
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The role of dipeptidyl peptidase-IV and homologous proteases in migration and invasion.
Fejfarová, Edita ; Rösel, Daniel (referee) ; Bušek, Petr (advisor)
Migration and invasion are processes which naturally occur in organism during embryogenesis, immune reactions or wound healing. These processes are very important factors in some serious diseases like rheumatoid arthritis and carcinogenesis. There is no doubt about contribution of proteases in these processes-many of them degrade extracellular matrix and thereby facilitate the movement of cells. While dipeptidylpeptidase-IV cleaves solely two amino acids from N-terminus so it is not considerably involved in ECM degradation. DPPIV and its homologues recognize peptides with proline on penultimate position, which causes resistance to ordinary types of proteases. Substrates of DPPIV and its activity homologues include chemokines implicated in signalling of migration - their cleavage and thus inactivation present DPPIV and DPPIV-like molecules as modulators of cell migration signalling in choriocacinoma, neuroblastoma, on Sézary cells or epithelial cells migrating in response to injury. Another activity of some DPPIV-like proteases is binding to the extracellular matrix proteins, when are helping in the attachment of cells and thus affect the migratory ability of the cells like ovarian cancer cells, prostate cancer cells, melanoma cells or kidney cells. Effects on migration and invasion have also...
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