Histogenesis‐specific expression of fibroblast activation protein and dipeptidylpeptidase‐IV in human bone and soft tissue tumours

Abstract

Aims:Fibroblast activation protein (FAP)/seprase and dipeptidylpeptidase-IV (DPP-IV)/CD26 are serine integral membrane proteases. They are involved in tissue remodelling, cancer invasion and metastases, mechanisms that are controversial. The aim was to identify cell types that express FAP and DPP-IV in human bone and soft tissue tumours, and to determine whether there are any correlations between the expression of FAP and DPP-IV and the malignant potential of tumours.Methods and results:This study analysed in situ expression in 25 malignant and 13 benign human bone and soft tissue tumours. Reverse transcriptase-polymerase chain reaction analyses confirmed mRNA expression of FAP and DPP-IV in all individuals. Immunohistochemistry using pre-fixed frozen sections revealed that FAP was positive in low-grade myofibroblastic sarcoma, the fibroblastic component of osteosarcomas, and malignant fibrous histiocytomas, but negative in Ewing’s sarcomas and rhabdomyosarcomas. DPP-IV showed similar immunohistochemical results. Among benign tumours, non-ossifying fibromas, desmoid tumours and chondroblastomas expressed both FAP and DPP-IV. Giant cells expressed DPP-IV in giant cell tumours.Conclusions:Our data suggest that FAP and DPP-IV are consistently expressed in bone and soft tissue tumour cells that are histogenetically related to activated fibroblasts and/or myofibroblasts, irrespective of their malignancy. DPP-IV is also expressed in monocyte–macrophage lineage cells.

Differential proteomic analysis of synovial fluid from rheumatoid arthritis and osteoarthritis patients

“…FAP has been shown to be expressed by synovial fibroblasts in both RA and OA patients [40]. Its expression has also been demonstrated in several bone tumors including low-grade myofibroblastic sarcoma and osteosarcomas [41]. In this study, it was found to be upregulated in OA synovial fluid by 5-fold.…”

Fibroblast activation protein

“…21 As to bone and soft tissue sarcomas, expression of FAP is clearly independent of the malignant potential of the tumor, and is rather related to the histogenesis of the tumor cells. 22 Based on the highly regulated expression and restricted distribution of FAP, it has been identified as a marker of reactive tumor stromal fibroblasts. Ossama Abbas et al 23 reported the differentiation of morpheaform/infiltrative basal cell carcinoma from desmoplastic trichoepithelioma using FAP as a marker.…”

Specific inhibition of fibroblast activation protein (FAP)-alpha prevents tumor progression in vitro

“…A hallmark of these activated fibroblasts is the expression of fibroblast activation protein alpha (FAP) [4,5]. This molecule is most prominently expressed on CAFs, but its surface expression has also been detected in bone and soft tissue sarcomas and in malignant melanomas [6,7]. It is a homodimeric type II transmembrane serine protease with postprolyl cleavage specificity and harbors both dipeptidase and endopeptidase activity [8][9][10][11].…”