Fibroblast activation protein (FAP) is a membrane-bound protease that is upregulated in a wide range of tumours and viewed as a marker of tumour-promoting stroma. Previously, we demonstrated increased FAP expression in glioblastomas and described its localisation in cancer and stromal cells. In this study, we show that FAP+ stromal cells are mostly localised in the vicinity of activated CD105+ endothelial cells and their quantity positively correlates with glioblastoma vascularisation. FAP+ mesenchymal cells derived from human glioblastomas are non-tumorigenic and mostly lack the cytogenetic aberrations characteristic of glioblastomas. Conditioned media from these cells induce angiogenic sprouting and chemotaxis of endothelial cells and promote migration and growth of glioma cells. In a chorioallantoic membrane assay, co-application of FAP+ mesenchymal cells with glioma cells was associated with enhanced abnormal angiogenesis, as evidenced by an increased number of erythrocytes in vessel-like structures and higher occurrence of haemorrhages. FAP+ mesenchymal cells express proangiogenic factors, but in comparison to normal pericytes exhibit decreased levels of antiangiogenic molecules and an increased Angiopoietin 2/1 ratio. Our results show that FAP+ mesenchymal cells promote angiogenesis and glioma cell migration and growth by paracrine communication and in this manner, they may thus contribute to glioblastoma progression.
- Publikační typ
- časopisecké články MeSH
- MeSH
- farmakoterapie klasifikace MeSH
- intrakraniální hypertenze diagnóza MeSH
- látky ovlivňující centrální nervový systém aplikace a dávkování klasifikace MeSH
- lidé MeSH
- nádory mozku * diagnostické zobrazování farmakoterapie klasifikace patologie terapie MeSH
- terapie klasifikace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
- MeSH
- diferenciální diagnóza MeSH
- lidé MeSH
- poruchy sluchu diagnóza klasifikace patofyziologie patologie MeSH
- Check Tag
- lidé MeSH
Dipeptidyl peptidase-IV (DPP-IV) and fibroblast activation protein-α (FAP) are speculated to participate in the regulation of multiple biological processes, because of their unique enzymatic activity, as well as by non-hydrolytic molecular interactions. At present, the role of DPP-IV and FAP in the development and progression of various types of tumors, including glioblastoma, is intensively studied, and their functional crosstalk is hypothesized. In this article, we describe the correlative expression of DPP-IV and FAP mRNA in primary cell cultures derived from human glioblastoma and associated expression dynamics of both molecules in astrocytoma cell lines depending on culture conditions. Although the molecular mechanisms of DPP-IV and FAP co-regulations remain unclear, uncoupled expression of transgenic DPP-IV and the endogenous FAP suggests that it occurs rather at the transcriptional than at the posttranscriptional level. Understanding of the expressional and functional coordinations of DPP-IV and FAP may help clarify the mechanisms of biological roles of both molecules in transformed astrocytic cells.
- MeSH
- buněčná diferenciace MeSH
- buněčné extrakty chemie MeSH
- buněčné kultury MeSH
- dipeptidylpeptidasa 4 genetika metabolismus MeSH
- enzymatické testy MeSH
- genetická transkripce MeSH
- lidé MeSH
- membránové proteiny genetika metabolismus MeSH
- messenger RNA genetika metabolismus MeSH
- neuroglie enzymologie metabolismus MeSH
- rekombinantní proteiny genetika metabolismus MeSH
- serinové endopeptidasy genetika metabolismus MeSH
- transformované buněčné linie MeSH
- želatinasy genetika metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- dipeptidylpeptidasa 4 farmakologie fyziologie klasifikace MeSH
- financování organizované MeSH
- leukocyty mononukleární enzymologie MeSH
- lidé MeSH
- osteoartróza enzymologie MeSH
- psoriatická artritida enzymologie patofyziologie MeSH
- revmatoidní artritida enzymologie patofyziologie MeSH
- synoviální tekutina enzymologie MeSH
- Check Tag
- lidé MeSH
