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Cancer-Associated Fibroblasts in the Breast Tumor Microenvironment

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Journal of Mammary Gland Biology and Neoplasia Aims and scope Submit manuscript

Abstract

Years of investigation have shed light on a theory in which breast tumor epithelial cells are under the effect of the stromal microenvironment. This review aims to discuss recent findings concerning the phenotypic and functional characteristics of cancer associated fibroblasts (CAFs) and their involvement in tumor evolution, as well as their potential implications for anti-cancer therapy. In this manuscript, we reviewed that CAFs play a fundamental role in initiation, growth, invasion, and metastasis of breast cancer, and also serve as biomarkers in the clinical diagnosis, therapy, and prognosis of this disease.

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Abbreviations

AT1R:

Angiotensin II (AngII) /AngII type I receptor

BM:

Bone marrow

CAF(s):

Cancer associated fibroblast(s)

CAV1:

Calveolin-1

CCL:

Chemokine ligand

CCR-2 C–C:

Chemokine receptor type 2

CD105:

Endoglin

CEACAM5:

Cells express antigen-related cell adhesion molecule 5

Chi3Li:

Chitinase 3-like 1

CSC:

Cancer stem cells

CTGF:

Connective tissue growth factor

CXCL C-X-C:

Motif chemokine ligand

CXCR4 C-X-C:

Motif chemokine receptor 4

CSPG:

Chondroitin sulfate proteoglycan

ECM:

Extracellular matrix

EGF:

Epidermal growth factor

EGFR:

Epidermal growth factor receptor

EMMPRIN:

Extracellular matrix metalloproteinase inducer

EMT:

Epithelial-mesenchymal transdifferentiation

ER:

Estrogen receptor

FAP:

Fibroblast activation protein

FGFR-1:

Fibroblast growth factor 1 receptor

FGF-β:

Basic fibroblast growth factor

FSP:

Fibroblast surface protein

Gas6:

Protein growth arrest-specific gene 6 protein

GemOE:

Geminin-overexpressing

HER2/neu:

Human epidermal growth factor receptor 2

HGF:

Hepatocyte growth factor

HIF-1α:

Hypoxia inducible factor-1α

HMGB1:

High mobility group box 1 protein

iCAFs:

Inflammatory’ CAFs

IGF:

Insulin growth factor

IGFR:

Insulin growth factor receptor

IL:

Interleukin

IL-R:

Interleukin receptor (R)

LOX:

Lysyl oxidase

LRRC15:

Leucine rich repeat containing 15

M-CSF:

Macrophage-colony stimulating factor

MDSC:

Myeloid-derived suppressor cells

MHC:

Major histocompatibility complex

MMP:

Metalloproteinases

MSC:

Mesenchymal stem cells

myoCAFs:

Myofibroblastic’ CAFs

NF-κB:

Nuclear factor-kappaβ

PD-1:

Programmed cell death protein 1

PDGF:

Platelet-derived growth factor

PDGFR:

Platelet-derived growth factor receptor

PDL-1:

Programmed death-ligand 1

PR:

Progesterone receptor

RAGE:

Receptor for advanced glycation end products

RANKL:

Receptor activator of nuclear factor-kappaβ ligand

ROS:

Reactive oxygen species

S100A4:

Calcium-binding protein

scRNA-seq:

Single-cell RNA sequencing

SDF-1:

Stromal-derived-factor-1

SLC39A8:

Solute carrier (SLC) 39A8

TAM:

Tumor-associated macrophages

TGF-β:

Transforming growth factor beta 1

TH1 T:

Lymphocyte helper 1

TIMP:

Tissue inhibitors of metalloproteinases

TNBC:

Triple negative breast cancer

TNF:

Tumor necrosis factor

TRAIL TNF:

Related apoptosis-inducing ligand

VEGF:

Vascular endothelial growth factor

α-SMA:

Alpha-smooth muscle actin

αFAP-PE38 FAP:

Targeting immunotoxin

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Acknowledgments

The authors thanks the National Agency of Scientific and Technological Promotion, Argentina; the National Council of Scientific and Technical Research, Argentina; Alberto Roemmers Foundation, Argentina; René Barón Foundation, Argentina and Williams Foundation, Argentina.

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Authors and Affiliations

  1. Laboratorio de Inmunohematología (IBYME) - Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Instituto de Biología y Medicina Experimental, Vuelta de Obligado 2490, CP, 1428, Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina

    María Belén Giorello, Francisco Raúl Borzone, Vivian Labovsky & Norma Alejandra Chasseing

  2. Laboratorio de Oncología Molecular y Nuevos Blancos Terapéuticos (IBYME) y Laboratorio de Inmunohematología (IBYME) - Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Instituto de Biología y Medicina Experimental, Vuelta de Obligado 2490, CP, 1428, Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina

    Flavia Valeria Piccioni

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  1. María Belén Giorello
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  3. Vivian Labovsky
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Contributions

María Belén Giorello, performed the literature search, organize and wrote the review, designed the figures. Francisco Raúl Borzone, critical revised the review. Vivian Labovsky, Critical revised the review. Flavia Valeria Piccioni, designed the figures and critical revised the review. Norma Alejandra Chasseing, had the idea. Performed the literature search, organize and wrote the review, designed the figures together with María Belén Giorello, both corresponding authors.

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Correspondence to María Belén Giorello or Norma Alejandra Chasseing.

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Giorello, M.B., Borzone, F.R., Labovsky, V. et al. Cancer-Associated Fibroblasts in the Breast Tumor Microenvironment. J Mammary Gland Biol Neoplasia 26, 135–155 (2021). https://doi.org/10.1007/s10911-020-09475-y

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