Table 1 The role of CAFs labeled by cancer-promoting markers in various kinds of cancer
From: What is new in cancer-associated fibroblast biomarkers?
Bio marker | Main origin | Description | Roles in cancers | |||
|---|---|---|---|---|---|---|
Pancreatic cancer | Breast cancer | Colorectal cancer | Lung cancer | |||
FAP | NFs | Type II intact membrane protein of serine protease family, including two subunits, α and β | Regulating accumulation of regulatory T cells, inhibition T cell activity, secreting CXCL12 and marginalized T cells through CXCL12-CXCR4 signaling, leading to tumor immunosuppression; Tumor promoting | Enriched in HER2-positive and triple-negative breast cancer stroma; expressing PD-1/2, which can bind to PD-1 expressed by T cells and inhibiting T cell activity | Interaction of FAP+ CAFs and SPP1+ macrophages contributing to desmoplastic tumor microenvironment and correlating with immunotherapy resistance | Correlating with the immunosuppressive TME status; predictive biomarker of resistance to PD-1 blockade; poor prognosis marker |
α-SMA | Cytoskeleton protein | α-SMAhighFAPhigh -myCAF α-SMAlowFAPlow -iCAF; relationship with survival is contradictory; inhibition IL-6 from α-SMA+CAF improving gemcitabine efficacy | Improving tumor growth via secretion of osteopontin; poor prognosis | Poor survival rates | MYH11+ α-SMA+ CAF and FAP+ α-SMA+ CAF driving T cell marginalization | |
POSTN | Stromal cell protein | Associated with highly cellular tumors and macrophage infiltrates and shorter overall survival | Playing an important role in carcinogenesis in situ and perhaps beyond for those cancers that become invasive | Correlated with tumor progression, lymph node and distant metastases, and poor clinical outcomes | Prognostic marker | |
PDGFRα/β | Tyrosine kinase receptor | Lymphatic invasion and lymph node metastasis; poor prognosis | PDGFRβ interacting with integrin A11 and leading to more aggressive behavior by activating JNK signaling | PDGFRβ+CAFs increasing the invasion and metastasis ability in a secreted glycoprotein stanniocalcin-1 dependent manner | Promoting recruitment of fibroblasts to the tumor infiltration front | |
FSP-1 | Small calcium binding protein | Identifying a unique population of fibroblasts with minimal overlap with markers for αSMA and PDGFRβ | Positive in primary breast cancer and in matched LNMs; inducing metastasis; associated with poor patient survival | Associated with poor patient survival | Lung premetastasis niche formation | |
Palladin | Actin binding protein | Secreting immunosuppressive cytokines to maintain the characteristics of iCAFs; producing functional desmoplastic ECMs to support cancer cell survival and proliferation; facilitating the invasion of cancer cells by remodeling ECM though regulating the small GTPase Cdc42; independent poor prognostic factor | As Akt1-specific substrate and regulating breast cancer cell migration | Correlated with reduced survival and relapse | Affecting the behavior of CAFs, leading to a pro-invasive henotype | |
Twist1 | A basic helix-loop-helix transcription factor | - | Tumor promoting; related to shorter survival | Promoting matrix stiffness | - | |
GFPT2 | Glutamine-Fructose-6-Phosphate Transaminase 2 | - | - | Regulating immunosuppression through JAK/STAT signaling pathway; associated with poorer pathological characteristics and OS | Regulating metabolic reprogramming and negatively correlates with prognosis | |
Vim | MSCs | Cytoskeletal protein | Poor survival; pro-tumoural profile | Associated with indices of poor prognosis | Independent prognostic factor for recurrence; related to shorter survival and chemoresistance | Promoting lung cancer metastasis by surrounding the cancer cells sprouting from primary tumor |
TNC | Extracellular matrix protein | Perineural invasion, high loco-regional recurrence, proliferation and invasion; poor prognosis | Related to LN metastasis and poorer outcome | Promoting EMT and proliferation; involved in tumor growth and metastasis via Hedgehog signaling; poor prognosis | Poorer clinical outcome biomarker | |
CD90 | GPI-anchored glycoprotein | Promoting pancreatic cancer development | - | Supporting the stemness of tumor cells and inducing an immune adaptive inflammatory response | Promoting tumor cell invasion; poor prognosis | |
CD10 | Metalloendoprotease | - | Supplying paracrine IL-8 and IL-6 through NF-κB signaling, forming a niche that protects CSC,leading to chemotherapy resistance and poor survival | - | Same to breast cancer | |
GPR77 | Non-G protein coupled receptor | - | - | - | ||
Galectin 1 | Stellate cells | β-galactoside binding protein | Tumor cell proliferation, angiogenesis, invasion, metastasis and inflammation | Immunosuppressive microenvironment; associated with high tumor grade and lymph node involvement; poor prognosis | Promoting CIC features and disease dissemination | Poorer clinical outcome biomarker |
AEBP1 | Epithelial cells | Multifunctional protein | - | - | Promoting proliferation, invasion, migration and metastasis by activating NF-κB signaling | An independent poor prognostic factor |
OPN | Not clear | secretory phosphoprotein | Promoting cancer stemness via SPP1-CD44 axis | Poor prognosis | Contributing to tumorigenesis by activation of the STAT3/PPARg pathway;poor prognosis | Promoting invasiveness and proliferation;poor prognosis |