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. 2021 Jun 10;6:218. doi: 10.1038/s41392-021-00641-0

Table 1.

Phenotype and heterogeneity of CAF

Tissue type Phenotype Markers Origin and/or function Ref.
BC (human) CAF-S1

CD29Med, FAPHi, FSP1Med,

α-SMAHi, PDGFRβMed-Hi, CAV-1Low

Regulatory of cancer invasion and immune response 58
CAF-S2

CD29Low, FAPNeg, FSP1Neg-Low,

α-SMANeg, PDGFRβNeg, CAV-1Neg

ND
CAF-S3 CD29Med, FAPNeg, FSP1Med-Hi, α-SMANeg-Low, PDGFRβMed, CAV-1Neg-Low ND
CAF-S4

CD29Hi, FAPNeg, FSP1Low-Med,

α-SMAHi, PDGFRβLow-Med, CAV-1Low

Regulatory of actin cytoskeleton and oxidative metabolism
OSCC (human) CAF-N KGF High fibroblast motility 60
CAF-D TGF-β1 Low fibroblast motility
NF HGF, MMP3 Lower tumor incidence
LC (human) Cluster 1 COL10A1 Showing a strong EMT signals 65
Cluster 2 COX4I2, ACTA2, MEF2C Regulatory of myogenesis and angiogenesis
Cluster 3 ND Upregulating collagen and ECM molecules expression
Cluster 4 PLA2G2A Similar to cluster 1
Cluster 5 MMP3 Low myogenesis and high mTOR expression
Cluster 6 FIGF Representing nonmalignant fibroblasts
Cluster 7 ND Similar to cluster 4 but differing in the glycolysis pathway
CRC (human) CAF-A MMP2, DCN, COL1A2 Regulatory of ECM remodeling and express FAP 66
CAF-B ACTA2, PDGFA, TAGLN Activation of cytoskeletal gene
NF MGP (ND) ND
HNSCC (human) CAF1 CTHRC1, COL1A1, POSTN, TPM4, MFAP2 (ND) Promoting cancer metastasis 67
CAF2 CFD, APOD, CXCL12, GPC3, SEPP1 (ND)
NF Depleted of markers for myofibroblasts and CAFs Resting fibroblasts
OC (human) FAP-high CAF FAP, TGF-β, COL11A1, SULF1, IL-6, CXCL12 Regulatory of cancer invasion and immune regulation 345
FAP-low CAF DLK1, TCF21, COLEC11 Regulatory of glucose homeostasis, lipid metabolism, etc.
NF COMP, SFRP2, GJB2 (ND) ND
BC (mouse) mCAF Fibulin-1, PDGFRα From resident fibroblast/regulatory of tumor immune response 57
vCAF Nidogen-2 From vasculature/promoting vascular development
cCAF Ki-67 Representing the proliferative segment of vCAF
dCAF SCRG1 From malignant cell/locating on tumor–stroma boundary
PDAC (mouse) myCAF α-SMA Adjacent to tumor cells and promoting desmoplasia 61
iCAF IL-6, LIF Locating away within stroma and promotes tumor progression
NF ND Pancreatic stellate cells
BC (mouse) Cluster 0 Ly6c1 From resident fibroblasts/promoting cancer progression and immune evasion 68
Cluster 1 α-SMA Promoting cancer development and progression
Cluster 2 Cdk1 Identifying as dividing cells
Cluster 3 Cd53 High transcriptional enrichment for desmin
Cluster 4 Crabp1 From Ly6c1high fibroblasts
Cluster 5 Cd74 Expressing MHC class II and regulatory of immune-modulatory
HCC (ND) Activated myofibroblast phenotype α-SMA, FAP, vimentin, vollagen 1α, PDGFRα, FN Maintaining and enhancing the stemness of HCC cells 398
Mesenchymal stromal cell phenotype CD90, CD73, CD105, CD29, CD44, CD166 Regulatory of immunosuppression

α-SMA alpha-smooth muscle actin, ACTA2 actin alpha 2, APOD apolipoprotein D, BC breast cancer, CAF cancer-associated fibroblast, CD clusters of differentiation, CAV-1 caveolin-1, Cdk1 cyclin-dependent kinases 1, CFD complement factor D, COL1 collagen type I, COLEC11 human collectin subfamily member 11, COX4I2 cytochrome c oxidase subunit 4I 2, Crabp1 cellular retinol-binding protein-I, CRC colon adenocarcinoma, CTHRC1 collagen triple helix repeat-containing protein 1, CXCL12 C–X–C motif chemokine 12, DCN decorin, DLK1 delta-like 1, ECM extracellular matrix, ELK3 ETS-domain protein, EMT epithelial–mesenchymal transition, FAP fibroblast activation protein, FIGF c-fos-induced growth factor, FN fibronectin, FOXO1 forkhead box protein O1, FSP1 fibroblast activation protein 1, GPC3 glypican-3, HCC hepatocellular carcinoma, HNSCC head and neck squamous cell carcinoma, HOXB2 homeobox 2, IL interleukin, KGF keratinocyte growth factor, LC lung cancer, LIF leukemia inhibitory factor, MEF2C myocyte enhancer factor 2C, MFAP2 microfibrillar associated protein 2, MMP matrix metalloproteinase, ND not determined, OC ovarian cancer, OSCC oral squamous cell carcinoma, PDAC pancreatic ductal adenocarcinoma, PDGF platelet-derived growth factor, PLA2G2A phospholipase A2 group IIA, POSTN periostin, SEPP1 selenoprotein P1, SCRG1 scrapie responsive protein 1, SULF1 sulfatase1, TAGLN transgelin, TCF21 transcription factor 21, TGF transforming growth factor, TPM4 tropomyosin-4