Biomolecules, Vol. 13, Pages 67: Cancer-Associated Fibroblast Heterogeneity, Activation and Function: Implications for Prostate Cancer

Identified in prostate cancerCAFs (generic)
(Human and mouse)Activated
fibroblasts
or
Activated
Myofibroblasts
or
Tumor-associated
fibroblasts (TAFs)Vimentin, αSMA, TGFβ, AR, TGFβR1/2,
FAP, CD90, CD105, COL1A1/2, FSP1, PDPN,
CD26, PDGFR-α/β, TNC, ASPN, POSTN, EGF, FGF7/2/10, IGF1, HGF, VEGF, OGN, Fibronectin, FBLN1, CTSK, PARVA, ZEB1, SPARCECM remodeling
Immune
Modulation
Angiogenesis
Paracrine
signaling to prostate cancer cells to promote growth, proliferation and survival.Resident
fibroblasts

Endothelial cells

Vascular
mural cells

Epithelial cells

Bone marrow-derived cells

Mesenchymal stem cells

[11,25,102,103,153]CD90+
(Human)Reactive stroma
fibroblasts
or
Tumorigenic fibroblasts
or
Tumor adjacent
fibroblastsCD90, ASPN, VEGF, FGF2, PATCH, TGFβ, IL6Tumorigenic
Unknown[77,103]CCL2+
(Human)CAF-0Vimentin, CD90, αSMA, PDPN, LRP1Low, GLRX,
PKMLow, CD63Low, TGFβ, CCL2CCL2 release to attract TAMsUnknown
(resident
fibroblasts predicted)[57]CXCL12+
(Human)CAF-1
or
SDF1+ CAFsVimentin, CD90Low, αSMA, PDPN, LRP1
GLRXLow, PKMLow, CD63Low, TGFβ, CXCL12CXCL12/SDF1α release to attract immune cells and activate AKT signaling via CXCR4 to promote cancer cell growth and survival Unknown, likely resident fibroblasts[57,154]CD105+
(Human and Mouse)Fibroblasts promoting neuroendocrine differentiation
or
endoglin+ CAFsCD105, αSMA, TNC, SFRP1
Promotes neuroendocrine differentiation of prostate adenocarcinoma
Unknown[6,155]TGFβR2+
(Mouse) TGFβR2, FGF2, Acta2, Tgfβ, VimentinAngiogenesis

Prostate cancer cell proliferation

Unknown (myofibroblasts predicted)[104]TGFβR2-
(Human and Mouse) TGFβR2 negative, αSMA, AR, Wnt3a, CXCL16, CXCL1
Promotes prostate cancer cell adhesion to bone collagen-I fibers to facilitate skeletal metastasis via CXCL1/CXCL16 secretionUnknown [133,156]FGF2+
(Human)Prostate cancer SC-9 cellsFGF2/7, TGFβhigh, VEGFhigh, COL1A1, TNC, ACTA2, EGF, IGF1
Predicted functions:
ECM remodeling; collagen
Deposition; paracrine TGFβ signaling to prostate cancer cells; angiogenesis Unknown[102]HGF+
(Human)Prostate cancer SC-8 cellsHGF, TGFβ, VEGF, TNC, ACTA2, EGF, FGF7, IGF1, Predicted functions: ECM remodeling and collagen deposition; paracrine TGFβ signaling to prostate cancer cells; angiogenesis.Unknown[102]FGF10+
(Mouse) FGF10Paracrine FGF10 signaling to prostate cancer cells causes increased AR expression and activated AKT.Mesenchymal cells [100]PDGFR+
(Human) PDGFRParacrine PDGFR signaling to prostate cancer cells increased cell motility and invasion.Resident
fibroblasts[95]PDGFRβ+
(Human)CAF-S1PDGFRβ, VIM, αSMA, CAV1, SPARC, ETS1Cell adhesion and angiogenesisUnknown (mesenchymal cells predicted)[36]PDGFRα+
(Human)CAF-S2PDGFRα, VIM, αSMA, CREB3L1, PLAGL1ECM production and angiogenesisUnknown (mesenchymal cells predicted)[36]Vimhi/αSMAhi
(Human)CAF-S3VIM, FAP, αSMA, TNC, CAV1, MAFB, HOXB2Fiber contraction to increase ECM stiffness and angiogenesisUnknown (myeloid cells predicted)[25,36,94]Bone marrow
derived
(Human and Mouse)Prostate cancer bone metastatic stromal cellsCOl1A1, αSMA, VIM, EPHA3, PTN, FSCN1, FN1, TGFβ1, TGFβR1/2, FGF2, CD109,
PDGFRβ Pro-tumorigenic

ECM remodeling

Skeletal system development

Cell adhesion

Angiogenesis

Wound healing

EMT

Wnt signaling

Bone marrow resident fibroblasts, bone-marrow-derived mesenchymal stem cells or hematopoietic stem cells[21]
Breast cancer: [56]
Gastric
cancer: [83]
Identified in other solid cancersMHCII+
(Human and Mouse)Antigen
presenting
fibroblastsMHCII, PDPN, CD74, COL1A1/2, PDPN, H2-AB1, FAP, VIMAntigen-specific CD4+ T cell
activation Resident
fibroblastsPancreatic cancer: [157]
LY6C+
(Human and Mouse)Inflammatory
fibroblastsLY6C, PDPN, IL-1R1, IL-6, COL1A41, HAS1, CXCL12, FAP, VIMActivates NF-kB and JAK/STAT signaling to
promote cancer cell proliferation.Resident
fibroblastsPancreatic cancer: [157,158,159]Endo180R+
(Human and Mouse)Matrix
remodeling
CAFs
or
uPARP+ CAFsEndo180R, PDGFRα, Fibulin-1, ACTA2, FAP, Vim, Sparc, PDGFRβ
PDPNECM remodeling

Collagen internalization and degradation

Angiogenesis

Resident
fibroblastsBreast cancer: [110,160,161]CD31+
(Human and Mouse)Vascular
CAFsNidogen-2, CD31, ACTA2, FSP1, PDGFRβ
Angiogenesis Pericytes or endothelial cellsBreast cancer: [110]
Pancreatic cancer: [88]Active CD31+
(Human and Mouse)Actively cycling vascular CAFsNidogen-2, Ki-67, CD31, ACTA2, PDGFRβProliferating CD31-CAFs.Perivascular cellsBreast cancer:
[110]Developmental
(Human and Mouse) SCRG1, Sparc, Mia,
TRLCell
differentiation

Tissue
development and morphogenesis

Predicted: mesenchymal stem cells, or
malignant
epithelial cellsBreast cancer:
[110]FSP1+
(Mouse)Fibroblast-like CAFsFSP-1, VEGFA, TNCBlood vessel remodeling

Apoptosis evasion

Resident
fibroblastsBreast cancer:
[93]
NG2+
(Human and Mouse) NG2, αSMA,
PDGFRβPredicted function:
Integrin-dependent PI3K/AKT signaling and
chemoresistanceUnknownBreast and pancreatic cancer:
[61,162]CD10+
(Human) CD10, GPR77Stimulates cancer stem cell activity via activation of NF-κB signalingUnknownBreast cancer: [163]

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