RETRACTED ARTICLE: The role of fibroblast activation protein in progression and development of osteosarcoma cells

Zhang, Liang; Yang, Li; Xia, Ziwei; Yang, Shi-Chang; Li, Wenhui; Liu, Bin; Yu, Ziqi; Gong, Peng; Yang, Yalin; Sun, Wei-Zong; Mo, Jing; Li, Gui-Shi; Wang, Tian-Yi; Wang, Kai

doi:10.1007/s10238-019-00591-6

Cited by 13 publications

(8 citation statements)

References 31 publications

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“…Dohi et al reported on a consistently high expression of FAP in bone and soft tissue tumor cells analyzing various sarcoma types like osteosarcoma, Ewing sarcoma, and rhabdomyosarcoma [ 12 ]. In osteosarcoma cells, significant inhibition of cell proliferation, migration, and invasion was observed after a knockdown of the serine protease [ 19 ], representing the importance of FAP for the malignant behavior of these tumors after its upregulation. Hereby, FAP most probably affects tumor stage and prognosis as demonstrated in a recently published meta-analysis by Liu et al: the authors observed that FAP expression was associated with an increased risk for nodal metastases, higher local tumor invasion, and poor survival [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

Novel FAP ligands enable improved imaging contrast in sarcoma patients due to FAPI-PET/CT

Koerber

Finck

Dendl

et al. 2021

Eur J Nucl Med Mol Imaging

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Purpose A high expression of fibroblast activation protein (FAP) was observed in multiple sarcomas, indicating an enormous potential for PET/CT using 68Ga-radiolabeled inhibitors of FAP (FAPI). Therefore, this retrospective study aimed to evaluate the role of the novel hybrid imaging probe for sarcomas as a first clinical evaluation. Methods A cohort of 15 patients underwent 68Ga-FAPI-PET/CT for staging or restaging. The acquisition of PET scans was performed 60 min after administration of 127 to 308 MBq of the tracer. The uptake of 68Ga-FAPI in malignant tissue as well as in healthy organs was quantified by standardized uptake values SUVmean and SUVmax. Results Excellent tumor-to-background ratios (> 7) could be achieved due to low background activity and high SUVmax in primary tumors (median 7.16), local relapses (median 11.47), and metastases (median 6.29). The highest uptake was found for liposarcomas and high-grade disease (range 18.86–33.61). A high SUVmax (> 10) was observed for clinically more aggressive disease. Conclusion These preliminary findings suggest a high potential for the clinical use of 68Ga-FAPI-PET/CT for patients diagnosed with sarcoma.

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Section: Discussionmentioning

confidence: 99%

Novel FAP ligands enable improved imaging contrast in sarcoma patients due to FAPI-PET/CT

Koerber

Finck

Dendl

et al. 2021

Eur J Nucl Med Mol Imaging

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“…[22] Conformably, FAP was supposed to be significantly associated with tumor size and clinical stage in osteosarcoma. [23] It has also been predicted to play a novel role in the attachment of synovial fibroblasts to cartilage, which further contributes to proteoglycan loss and cartilage degradation. [24] THY1 also known as CD90, is widely regarded as a cell surface marker for sorting a subpopulation of fibroblasts in the heart.…”

Section: Discussionmentioning

confidence: 99%

Identifying immune cell infiltration and diagnostic biomarkers in heart failure and osteoarthritis by bioinformatics analysis

Wen¹,

Liu

Qin

et al. 2023

Medicine

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Heart failure (HF) and osteoarthritis (OA) are medical conditions that can significantly impact daily activities. Evidence has shown that HF and OA may share some pathogenic mechanisms. However, the underlying genomic mechanisms remain unclear. This study aimed to explore the underlying molecular mechanism and identify diagnostic biomarkers for HF and OA. With the cutoff criteria of fold change (FC) > 1.3 and P < .05, 920, 1500, 2195, and 2164 differentially expressed genes (DEGs) were identified in GSE57338, GSE116250, GSE114007, and GSE169077, respectively. After making the intersection of DEGs, we obtained 90 upregulated DEGs and 51 downregulated DEGs in HF datasets and 115 upregulated DEGs and 75 downregulated DEGs in OA datasets. Afterward, we conducted genome ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, protein-protein interaction (PPI) networks, and hub genes screening based on DEGs. Then, 4 common DEGs (fibroblast activation protein alpha [FAP], secreted frizzled-related protein 4 (SFRP4), Thy-1 cell surface antigen (THY1), matrix remodeling associated 5 [MXRA5]) between HF and OA were screened and validated in GSE5406 and GSE113825 datasets, based on which we established the support vector machine (SVM) models. The combined area under the receiver operating characteristic curve (AUC) of THY1, FAP, SFRP4, and MXRA5 in the HF training and test sets reached 0.949 and 0.928. While in the OA training set and test set, the combined AUC of THY1, FAP, SFRP4, and MXRA5 reached 1 and 1, respectively. The analysis of immune cells in HF revealed high levels of dendritic cell (DC), B cells, natural killer T cell (NKT), Type 1 regulatory T cell (Tr1), cytotoxic T cell (Tc), exhausted T cell (Tex), and mucosal-associated invariant T cell (MAIT), while displaying lower levels of monocytes, macrophages, NK, CD4 + T, gamma delta T (γδ T), T helper type 1 (Th1), T helper type 2 (Th2), and effector memory T cell (Tem). Moreover, the 4 common DEGs were positively correlated with DCs and B cells and negatively correlated with γδ T. In OA patients, the abundance of monocyte, macrophage, CD4 + naïve, and natural T regulatory cell (nTreg) was higher, while the infiltration of CD8 + T, γδ T, CD8 + naïve, and MAIT was lower. The expression of THY1 and FAP was significantly correlated with macrophage, CD8 + T, nTreg, and CD8 + naïve. SFRP4 was correlated with monocyte, CD8 + T, γδ T, CD4 + naïve, nTreg, CD8 + naïve and MAIT. MXRA5 was correlated with macrophage, CD8 + T, nTreg and CD8 + naïve. FAP, THY1, MXRA5, and SFRP4 may be diagnostic biomarkers for both HF and OA, and their correlation with immune cell infiltrations suggests shared immune pathogenesis.

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“…A clinical and in vivo study showed that high expression of FAP in osteosarcoma is significantly associated with the tumor size and clinical stage. They revealed that the knockdown of FAP remarkably blocked the proliferation, migration, and invasion of osteosarcoma cells in vitro , suppressing mouse tumor growth and metastasis via the AKT signaling pathway [ 75 ]. FAP promotes the growth, adhesion, and migration of lung Squamous Cell Carcinoma.…”

Section: Introductionmentioning

confidence: 99%

The Prognostic and therapeutic value and clinical implications of fibroblast activation protein-α as a novel biomarker in colorectal cancer

et al. 2023

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The identification of contributing factors leading to the development of Colorectal Cancer (CRC), as the third fatal malignancy, is crucial. Today, the tumor microenvironment has been shown to play a key role in CRC progression. Fibroblast-Activation Protein-α (FAP) is a type II transmembrane cell surface proteinase expressed on the surface of cancer-associated fibroblasts in tumor stroma. As an enzyme, FAP has di- and endoprolylpeptidase, endoprotease, and gelatinase/collagenase activities in the Tumor Microenvironment (TME). According to recent reports, FAP overexpression in CRC contributes to adverse clinical outcomes such as increased lymph node metastasis, tumor recurrence, and angiogenesis, as well as decreased overall survival. In this review, studies about the expression level of FAP and its associations with CRC patients' prognosis are reviewed. High expression levels of FAP and its association with clinicopathological factors have made as a potential target. In many studies, FAP has been evaluated as a therapeutic target and diagnostic factor into which the current review tries to provide a comprehensive insight.

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RETRACTED ARTICLE: The role of fibroblast activation protein in progression and development of osteosarcoma cells

Cited by 13 publications

References 31 publications

Novel FAP ligands enable improved imaging contrast in sarcoma patients due to FAPI-PET/CT

Novel FAP ligands enable improved imaging contrast in sarcoma patients due to FAPI-PET/CT

Identifying immune cell infiltration and diagnostic biomarkers in heart failure and osteoarthritis by bioinformatics analysis

The Prognostic and therapeutic value and clinical implications of fibroblast activation protein-α as a novel biomarker in colorectal cancer

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