Short Communication - Journal of Biochemistry and Biotechnology (2023) Volume 6, Issue 3
Fibroblast Activation Protein (FAP): Unraveling the Enigma of Tumor-Stromal Interactions
Department of Medicine, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan .
- *Corresponding Author:
- Jinchu Liu
Department of Medicine
Taipei Medical University-Shuang Ho Hospital
Received:29-May-2023,Manuscript No. AABB-23-104223;Editor assigned: 31-May-2023, PreQC No. AABB-23-104223 (PQ);Reviewed:15-Jun-2023, QC No. AABB-23-104223;Revised:20-Jun-2023, Manuscript No. AABB-23-104223 (R); Published:26-Jun-2023, DOI:10.35841/ aabb-6.3.142
Citation: Liu J. Fibroblast Activation Protein (FAP): Unraveling the enigma of tumor-stromal interactions. J Biochem Biotech 2023;6(3):142
Fibroblast Activation Protein (FAP) is best known for its heightened expression in tumour stroma. This atypical serine protease has dipeptidyl peptidase and endopeptidase activities, cleaving substrates at a post-proline bond. FAP expression is difficult to detect in non-diseased adult organs, but is greatly upregulated in sites of tissue remodelling, which include liver fibrosis, lung fibrosis, atherosclerosis, arthritis, tumours and embryonic tissues. Due to its restricted expression pattern and dual enzymatic activities, FAP is emerging as a unique therapeutic target. However, methods to exploit and target this protease are advancing more rapidly than knowledge of the fundamental biology of FAP. This review highlights this imbalance, emphasising the need to better define the substrate repertoire and expression patterns of FAP to elucidate its role in biological and pathological processes.
Collagen, Degradomics, Dipeptidyl peptidase, Endopeptidase, Exosite, Protease.
In the complex microenvironment of tumors, numerous cellular players contribute to the progression and metastasis of cancer. One such key player is fibroblast activation protein (FAP), a cell surface glycoprotein expressed on the surface of cancer-associated fibroblasts (CAFs). FAP has emerged as a fascinating target for cancer research due to its unique properties and potential implications in diagnosis, prognosis, and therapy. In this article, we delve into the realm of FAP and explore its role in the tumor-stromal interactions. FAP expression under physiological conditions is very low in the majority of adult tissues. FAP is nevertheless expressed during embryonic development, and in adults in pancreatic alpha cells in multipotent bone marrow stromal cells (BM-MSC) and uterine stroma .
Understanding Fibroblast Activation Protein (FAP)
Fibroblast activation protein (FAP), encoded by the FAP gene, is a type II integral membrane protein belonging to the serine protease family. Originally identified on fibroblasts in the reactive stroma of healing wounds, FAP gained prominence for its overexpression in the tumor microenvironment, particularly in the stroma of epithelial malignancies. FAP is commonly associated with tumor-associated fibroblasts (TAFs), which are activated fibroblasts that play a critical role in the tumor microenvironment .
Functions and implications in cancer
FAP has been implicated in various aspects of tumor progression, metastasis, and immune evasion. Its expression in the tumor stroma is often associated with poor prognosis in many cancers. Several studies have shown that FAP promotes tumor growth by modulating the extracellular matrix (ECM) through proteolytic activity. FAP possesses both dipeptidyl peptidase and endopeptidase enzymatic functions, enabling it to degrade ECM components and remodel the tumor microenvironment. Furthermore, FAP's proteolytic activity can also promote angiogenesis, a process crucial for tumor survival and metastasis. By activating pro-angiogenic factors and promoting endothelial cell migration, FAP contributes to the formation of new blood vessels that sustain tumor growth .
Diagnostic and therapeutic potential
Given its unique expression pattern and functional relevance in cancer, FAP has garnered interest as a potential diagnostic and therapeutic target. FAP expression has been detected in various types of cancer, including breast, lung, pancreatic, colorectal, and prostate cancer, making it a promising biomarker for cancer diagnosis and monitoring.
Imaging modalities such as positron emission tomography (PET) have been utilized to visualize FAP expression in tumors. This imaging approach allows for non-invasive detection of FAP-positive lesions and can aid in treatment planning and monitoring of therapeutic response. Therapeutically, FAP has attracted attention as a target for novel anti-cancer strategies. Several approaches are being explored, including small molecule inhibitors, antibody-drug conjugates, and immunotherapeutic interventions. Preclinical studies targeting FAP have shown promising results, highlighting the potential of FAP-directed therapies to enhance anti-tumor immune responses and improve treatment outcomes..
Fibroblast activation protein (FAP) represents a fascinating piece of the intricate puzzle that is the tumor microenvironment. Its distinct expression pattern, functional roles in tumor-stromal interactions, and implications in cancer progression make it a captivating subject of research and therapeutic exploration. Understanding the precise mechanisms by which FAP influences tumor growth, angiogenesis, and immune evasion holds the key to developing effective strategies to combat cancer.
- Burgess WH, Maciag The heparin-binding (fibroblast) growth factor family of proteins. Annu Rev Biochem. 1989;58(1):575-602.
- Fitzgerald AA, Weiner LM.The role of fibroblast activation protein in health and malignancy.. The role of fibroblast activation protein in health and malignancy.
- Liu R, Li H, Liu L, et al.Fibroblast activation protein: A potential therapeutic target in cancer Fibroblast activation protein: A potential therapeutic target in cancer.
- Pure E, Blomberg R.Pro-tumorigenic roles of fibroblast activation protein in cancer: Back to the basics.JPro-tumorigenic roles of fibroblast activation protein in cancer: Back to the basics.
- Olsen SK, Garbi M, Zampieri N, et al.Fibroblast growth factor (FGF) homologous factors share structural but not functional homology with FGFs.. J Biol Chem. 2003;278(36):34226-36.