P04.28 Effect of fibroblast activation protein-expressing stromal cells from human glioblastomas on glioma and endothelial cells
| Autor: | Petr Vymola, Aleksi Sedo, K Vlasicova, Rosana Mateu, Petr Busek, Eva Balaziova |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Cancer Research
Tumor microenvironment congenital hereditary and neonatal diseases and abnormalities Stromal cell Endothelium Chemistry Angiogenesis medicine.medical_treatment Growth factor medicine.disease Poster Presentations Cytokine medicine.anatomical_structure Oncology Fibroblast activation protein alpha Glioma Cancer research medicine Neurology (clinical) neoplasms |
| Zdroj: | Europe PubMed Central |
| Popis: | BACKGROUND: Fibroblast activation protein (FAP) is a protease selectively expressed in a number of extracranial cancers especially in cancer associated fibroblasts (CAF). CAF play an important role in the pathogenesis of malignant tumors through extracellular matrix remodeling, secretion of growth factors and cytokines, and promotion of angiogenesis and intratumoral immunosuppression. Glioblastomas (GBMs) have a unique composition of the tumor microenvironment and whether CAF are present in these tumors remains controversial. We have recently shown that FAP is upregulated in a subgroup of GBMs and is expressed in both cancer and stromal cells. The role of FAP+ stromal cells in GBM is however unknown. MATERIAL AND METHODS: FAP positive stromal cells were isolated using magnetic activated cell sorting (MACS), and cultured in pericyte media. Expression of FAP and other phenotypic markers was assessed by immunocytochemistry. Conditioned media were prepared and used as a chemoattractant in a transwell migration assay. Cell growth was analyzed using the XTT assay, angiogenesis was evaluated using a 3D angiogenesis assay in type I collagen gel. A cytokine array was used to analyze soluble mediators released by FAP+ stromal cells. RESULTS: FAP+ stromal cells were isolated from several human GBMs and characteristically expressed mesenchymal (TE-7, PDGFR, SMA), but not endothelial (vWF) or glial (GFAP) markers. Conditioned media from these FAP+ cells enhanced the migration of glioma and endothelial cells and enhanced endothelial sprouting in a 3D angiogenesis assay. Part of the conditioned media had a mild growth promoting effect on endothelial and glioma cells. Using cytokine arrays, we identified several chemokines, growth factors and angiogenic factors produced by these FAP+ stromal cells. CONCLUSION: Our data demonstrate that FAP+ mesenchymal cells analogous to cancer associated fibroblasts participate on multidirectional interactions among cell subpopulations in human glioblastomas mediated, at least in part, by soluble factors. These FAP+ stromal cells may contribute to the invasive growth and neoangiogenesis in glioblastoma. ACKNOWLEDGEMENT: Ministry of Health of CR grant 15-31379A, Progres Q28/1LFUK and grant LM2015064 of the EATRIS-CZ. |
| Databáze: | OpenAIRE |
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