Pro-tumorigenic roles of fibroblast activation protein in cancer: back to the basics

Puré, Ellen; Blomberg, Rachel

doi:10.1038/s41388-018-0275-3

Cited by 243 publications

(208 citation statements)

References 135 publications

(194 reference statements)

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“…FAP has high expression in HSOC patients in both Chinese population (over 60% in our study) and other ethnics (over 50%) (30). In addition, performance of therapeutic targeting at FAP also suggests its effectiveness for cancers (31). Therefore, FAP could be a potential biomarker for drug delivery or even direct therapy for HSOC.…”

Section: Discussionmentioning

confidence: 53%

High expression of Fibroblast activation protein (FAP) predicts poor outcome in high-grade serous ovarian cancer

Xue

Rong

et al. 2020

Preprint

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Abstract Background: High-grade serous ovarian cancer (HSOC) is a fatal form of ovarian cancer. Previous studies indicated some potential biomarkers for clinical evaluation of HSOC prognosis. However, there is a lack of systematic analysis of different expression genes (DEGs) to screen and detect significant biomarkers of HSOC. Method and materials: TCGA database was conducted to analyze relevant genes expression in HSOC. Outcomes of candidate genes expression, including overall survival (OS) and progression-free survival (PFS), were calculated by Cox regression analysis for hazard rates (HR). Histopathological investigation of the identified genes was carried out in 151 Chinese HSOC patients to validate gene expression in different stages of HSOC. Results: Of all 57,331 genes that were analyzed, FAP was identified as the only novel gene that significantly contributed to both OS and PFS of HSOC. In addition, FAP had a consistent expression profile between carcinoma-paracarcinoma and early-advanced stages of HSOC. Immunological tests in paraffin section also confirmed that up-regulation of FAP was present in advanced stage HSOC patients. Prediction of FAP network association suggested that FN1 could be a potential downstream gene which further influenced HSOC survival. Conclusions: High-level expression of FAP was associated with poor prognosis of HSOC via FN1 pathway.

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Section: Discussionmentioning

confidence: 53%

High expression of Fibroblast activation protein (FAP) predicts poor outcome in high-grade serous ovarian cancer

Xue

Rong

et al. 2020

Preprint

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“…CD90 has been widely used for the identification or isolation of dermal fibroblasts 18,20,21 . However, we have demonstrated that besides CD90+ fibroblasts, human dermis also harbors a CD90 fibroblast population expressing FAP 16 , which has been established as a marker for activated fibroblasts and cancer-associated fibroblasts (CAFs) 22,23,24,25 . Importantly, we were able to identify three fibroblast subpopulations FAP biopsies from all healthy human donors.…”

Section: Discussionmentioning

confidence: 99%

Isolation of Papillary and Reticular Fibroblasts from Human Skin by Fluorescence-activated Cell Sorting

Korosec

Frech

Lichtenberger

2019

JoVE

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Citation: Korosec, A., Frech, S., Lichtenberger, B.M. Isolation of Papillary and Reticular Fibroblasts from Human Skin by Fluorescence-activated Cell Sorting. AbstractFibroblasts are a highly heterogeneous cell population implicated in the pathogenesis of many human diseases. In human skin dermis, fibroblasts have traditionally been attributed to the superficial papillary or lower reticular dermis according to their histological localization. In mouse dermis, papillary and reticular fibroblasts originate from two different lineages with diverging functions regarding physiological and pathological processes and a distinct cell surface marker expression profile by which they can be distinguished. Importantly, evidence from explant cultures from superficial and lower dermal layers suggest that at least two functionally distinct dermal fibroblasts lineages exist in human skin dermis as well. However, unlike for mouse skin, cell surface markers enabling the discrimination of different fibroblast subsets have not yet been established for human skin. We developed a novel protocol for the isolation of human papillary and reticular fibroblast populations via fluorescence-activated cell sorting (FACS) using the two cell surface markers Fibroblast Activation Protein (FAP) and Thymocyte antigen 1 (Thy1)/CD90. This method enables the isolation of pure fibroblast subsets without in vitro manipulation, which was shown to affect gene expression, thus permitting accurate functional analysis of human dermal fibroblast subsets in regard to tissue homeostasis or disease pathology.

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“…Dies macht FAP zu einer potenziellen Zielstruktur für die molekulare Bildgebung und Therapie einer großen Zahl von Tumorerkrankungen [51]. Bei verschiedenen Tumorerkrankungen ist eine hohe FAP-Expression von CAFs mit einer schlechteren Prognose assoziiert [51,52]. Ein Mechanismus dafür ist möglicherweise, dass der Abbau der extrazellulären Matrix die Invasion von Tumorzellen in das umgebende Gewebe erleichtert [53].…”

Section: Fap/fapi-04unclassified

Neue Entwicklungen auf dem Gebiet der Theranostik

Weber

2019

Nuklearmediziner

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ZusammenfassungDiese Übersichtsarbeit stellt neue Radiopharmaka für die Tumordiagnostik und -therapie vor, die erfolgversprechende präklinische Ergebnisse gezeigt haben und aktuell in klinischen Studien untersucht werden. Dazu gehören mehrere radioaktiv markierte Antikörper wie 131I-Omburtamab, ein gegen das B7-H3-Protein gerichteter Antikörper, der zur Therapie von Neuroblastomen eingesetzt wird; HuMab-5B1, ein 89Zr/177Lu markierter Antikörper zur Therapie von CA19-9 exprimierenden Tumoren und 177Lu-Lilotomab, ein Antikörper gegen das Oberflächenantigen CD37 für die Therapie von B-Zell-Lymphomen. Weitere Beispiele sind der Neurotensin Rezeptor Ligand 111In/177Lu-3B-227 für die Diagnostik und Therapie von verschiedenen Tumorerkrankungen, insbesondere Adenokarzinomen des Pankreas und der Phospholipidether 131I/124I-CLR1404, der wahrscheinlich aufgrund einer veränderten Membranstruktur in verschiedenen Tumorzelltypen angereichert wird. Neben diesen, von Tumorzellen exprimierten Zielstrukturen wird auch das Fibroblasten Aktivierungs Protein (FAP), das im Tumorstroma gebildet wird, als Zielstruktur für die Bildgebung und Therapie eingesetzt (68Ga/90Y-FAPI-04). Diese neuen Radiopharmaka haben das Potenzial für die Therapie einer ganzen Reihe von Tumorerkrankungen und ihre Effektivität sollte in systematischen Studien untersucht werden.

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Pro-tumorigenic roles of fibroblast activation protein in cancer: back to the basics

Cited by 243 publications

References 135 publications

High expression of Fibroblast activation protein (FAP) predicts poor outcome in high-grade serous ovarian cancer

High expression of Fibroblast activation protein (FAP) predicts poor outcome in high-grade serous ovarian cancer

Isolation of Papillary and Reticular Fibroblasts from Human Skin by Fluorescence-activated Cell Sorting

Neue Entwicklungen auf dem Gebiet der Theranostik

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