Table 1 List of commonly used biomarkers for CAFs
Marker | Cell origin | Biological effects | Effects on tumors | Clinical application |
|---|---|---|---|---|
Neutral biomarkers with dual functions | ||||
α-SMA | Normal fibroblasts, quiescent stellate cells, smooth muscle cells | Cell contractility, structure and integrity, desmoplasia | Tumor proliferation, immunosuppressive; protection mechanism, impeding drug delivery | Preclinical trials by targeting α-SMA directly failed; prognostic indicator |
S100A4 | Normal fibroblasts, epithelial cells, endothelial cells | Cell motility, tissue fibrosis | Promoting metastasis, immune evasion; immune surveillance and response | Unknown |
Accomplices: pro-tumorigenesis biomarkers | ||||
FAP | Normal fibroblasts, quiescent stellate cells, CD45+ immune cells | ECM remodeling, fibrogenesis, serine protease activity | Tumor progression and metastasis, shaping the immunosuppressive TME | Preclinical trials (antibody, inhibitor, DNA vaccination, oncolytic adenovirus, CAR-T); phase II clinical trials (PT-100, sibrotuzumab) failed; prognostic indicator |
PDGFRα/β | Normal fibroblasts, vascular smooth muscle cells, pericytes | Receptor tyrosine kinase activity | Immunomodulation, M2 polarization, angiogenesis | Dasatinib normalizes CAFs; targeting Saa3 in PDGFRα+ CAFs; prognostic indicator |
PDPN | Endothelial cells | Cell motility and adhesion | Immunosuppressive | Unknown |
CD70 | T and B lymphocytes, mature dendritic cells | T cell function regulation | Immunosuppressive, tumor cell migration, T cell exhaustion | Prognostic indicator |
Vimentin | Epithelial cells, endothelial cells | Cell motility, structure and integrity | Tumor invasion | Unknown |
GPR77 | Polymorphonuclear neutrophils | Complement activation, pro-inflammatory signaling | Sustaining cancer stemness, cancer formation, chemoresistance | Neutralizing anti-GPR77 antibody abolishes tumor formation in a PDX model |
CD10 | BMSCs, pre-B lymphocytes | Metalloendoprotease | Sustaining cancer stemness, cancer formation, chemoresistance | Unknown |
CD74 | Normal fibroblasts, monocytes/macrophages, epithelial cells | MHC II chaperone, protein trafficking | Immunomodulation | Unknown |
Defenders: tumor-suppressive biomarkers | ||||
CD146 | Endothelial cells | Cell adhesion | Maintaining ER expression, sensitive to tamoxifen | Prognostic indicator; Considered as a drug? |
CAV1 | Normal fibroblasts, endothelial cells, adipocytes | Structure component, cell signaling and transport | CAV1low associated with poor prognosis | Prognostic indicator |
Saa3− | Smooth muscle cells, adipocytes | Collagenase production | PDGFRα+Saa3− CAF impairing tumor proliferation | Targeting Saa3 in PDGFRα+ CAF; prognostic indicator |