Fibroblast activation protein as a potential theranostic target in brain metastases of diverse solid tumours
Jazyk angličtina Země Anglie, Velká Británie Médium print-electronic
Typ dokumentu časopisecké články
PubMed
37419841
DOI
10.1016/j.pathol.2023.05.003
PII: S0031-3025(23)00137-X
Knihovny.cz E-zdroje
- Klíčová slova
- Brain metastases, cancer-associated fibroblasts, fibroblast activation protein, theranostics, tumour stroma,
- MeSH
- fibroblasty patologie MeSH
- individualizovaná medicína MeSH
- karcinom z renálních buněk * patologie MeSH
- kvalita života MeSH
- lidé MeSH
- membránové proteiny metabolismus MeSH
- nádorové mikroprostředí MeSH
- nádory ledvin * patologie MeSH
- nádory mozku * patologie MeSH
- serinové endopeptidasy metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- membránové proteiny MeSH
- serinové endopeptidasy MeSH
Brain metastases are a very common and serious complication of oncological diseases. Despite the vast progress in multimodality treatment, brain metastases significantly decrease the quality of life and prognosis of patients. Therefore, identifying new targets in the microenvironment of brain metastases is desirable. Fibroblast activation protein (FAP) is a transmembrane serine protease typically expressed in tumour-associated stromal cells. Due to its characteristic presence in the tumour microenvironment, FAP represents an attractive theranostic target in oncology. However, there is little information on FAP expression in brain metastases. In this study, we quantified FAP expression in samples of brain metastases of various primary origin and characterised FAP-expressing cells. We have shown that FAP expression is significantly higher in brain metastases in comparison to non-tumorous brain tissues, both at the protein and enzymatic activity levels. FAP immunopositivity was localised in regions rich in collagen and containing blood vessels. We have further shown that FAP is predominantly confined to stromal cells expressing markers typical of cancer-associated fibroblasts (CAFs). We have also observed FAP immunopositivity on tumour cells in a portion of brain metastases, mainly originating from melanoma, lung, breast, and renal cancer, and sarcoma. There were no significant differences in the quantity of FAP protein, enzymatic activity, and FAP+ stromal cells among brain metastasis samples of various origins, suggesting that there is no association of FAP expression and/or presence of FAP+ stromal cells with the histological type of brain metastases. In summary, we are the first to establish the expression of FAP and characterise FAP-expressing cells in the microenvironment of brain metastases. The frequent upregulation of FAP and its presence on both stromal and tumour cells support the use of FAP as a promising theranostic target in brain metastases.
Department of Neurosurgery Na Homolce Hospital Prague Czech Republic
Department of Pathology Na Homolce Hospital Prague Czech Republic
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