Cancer‐associated fibroblasts: Secretions, interactions, and therapy

Farhood, Bagher; Najafi, Masoud; Mortezaee, Keywan

doi:10.1002/jcb.27703

Cited by 72 publications

(59 citation statements)

References 67 publications

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“…In this present study we provide novel insights into the ability of estrogens to regulate miR-338-3p expression and function through GPER in ER-negative breast cancer cells and cancer associated fibroblasts (CAFs), which are main components of the tumor microenvironment [ 35 , 36 ]. On the basis of our findings miR-338-3p may be included among the miRNAs involved in breast tumor development.…”

Section: Introductionmentioning

confidence: 99%

miR-338-3p Is Regulated by Estrogens through GPER in Breast Cancer Cells and Cancer-Associated Fibroblasts (CAFs)

Vivacqua

Sebastiani

Miglietta

et al. 2018

Cells

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Estrogens acting through the classic estrogen receptors (ERs) and the G protein estrogen receptor (GPER) regulate the expression of diverse miRNAs, small sequences of non-coding RNA involved in several pathophysiological conditions, including breast cancer. In order to provide novel insights on miRNAs regulation by estrogens in breast tumor, we evaluated the expression of 754 miRNAs by TaqMan Array in ER-negative and GPER-positive SkBr3 breast cancer cells and cancer-associated fibroblasts (CAFs) upon 17β-estradiol (E2) treatment. Various miRNAs were regulated by E2 in a peculiar manner in SkBr3 cancer cells and CAFs, while miR-338-3p displayed a similar regulation in both cell types. By METABRIC database analysis we ascertained that miR-338-3p positively correlates with overall survival in breast cancer patients, according to previous studies showing that miR-338-3p may suppress the growth and invasion of different cancer cells. Well-fitting with these data, a miR-338-3p mimic sequence decreased and a miR-338-3p inhibitor sequence rescued the expression of genes and the proliferative effects induced by E2 through GPER in SkBr3 cancer cells and CAFs. Altogether, our results provide novel evidence on the molecular mechanisms by which E2 may regulate miR-338-3p toward breast cancer progression.

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Section: Introductionmentioning

confidence: 99%

miR-338-3p Is Regulated by Estrogens through GPER in Breast Cancer Cells and Cancer-Associated Fibroblasts (CAFs)

Vivacqua

Sebastiani

Miglietta

et al. 2018

Cells

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“…However, CAFs also play an important role in matrix degradation by secreting matrix enzymes such as MMPs, which engages cancer cells to reshape their morphology and breakthrough basement membrane. Both deposition and degradation of ECM induced by CAFs are cancer promoting and CAFs could be essential target for cancer therapies 41 …”

Section: Composition and Function Of The Tmementioning

confidence: 99%

Modifying the tumour microenvironment and reverting tumour cells: New strategies for treating malignant tumours

et al. 2020

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The tumour microenvironment (TME) plays a pivotal role in tumour fate determination. The TME acts together with the genetic material of tumour cells to determine their initiation, metastasis and drug resistance. Stromal cells in the TME promote the growth and metastasis of tumour cells by secreting soluble molecules or exosomes. The abnormal microenvironment reduces immune surveillance and tumour killing. The TME causes low anti‐tumour drug penetration and reactivity and high drug resistance. Tumour angiogenesis and microenvironmental hypoxia limit the drug concentration within the TME and enhance the stemness of tumour cells. Therefore, modifying the TME to effectively attack tumour cells could represent a comprehensive and effective anti‐tumour strategy. Normal cells, such as stem cells and immune cells, can penetrate and disrupt the abnormal TME. Reconstruction of the TME with healthy cells is an exciting new direction for tumour treatment. We will elaborate on the mechanism of the TME to support tumours and the current cell therapies for targeting tumours and the TME—such as immune cell therapies, haematopoietic stem cell (HSC) transplantation therapies, mesenchymal stem cell (MSC) transfer and embryonic stem cell‐based microenvironment therapies—to provide novel ideas for producing breakthroughs in tumour therapy strategies.

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“…Cancer-associated fibroblasts (CAFs) are the dominant stromal cell population in many solid tumours [ 8 , 9 , 10 ] and form the focus of the present review. CAFs exhibit several functions in cancer: promoting malignant cell growth through bidirectional signalling with both tumour cells and other cells within the TME [ 11 , 12 ]; facilitating the process of metastasis through synthesis and remodelling of extracellular matrix (ECM) components and secretion of angiogenic factors such as vascular endothelial growth factor (VEGF) [ 11 , 13 ]; sustaining cancer cell bioenergetics through release of CAF-derived metabolites [ 14 , 15 ]; contributing to tumour chemoresistance [ 3 , 16 ]; and promoting evasion of immune surveillance [ 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

Cancer-Associated Fibroblast Mediated Inhibition of CD8+ Cytotoxic T Cell Accumulation in Tumours: Mechanisms and Therapeutic Opportunities

Freeman

Mielgo

2020

Cancers

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The tumour microenvironment (TME) is the complex environment in which various non-cancerous stromal cell populations co-exist, co-evolve and interact with tumour cells, having a profound impact on the progression of solid tumours. The TME is comprised of various extracellular matrix (ECM) proteins in addition to a variety of immune and stromal cells. These include tumour-associated macrophages, regulatory T cells (Tregs), myeloid-derived suppressor cells, as well as endothelial cells, pericytes and cancer-associated fibroblasts (CAFs). CAFs are the most abundant stromal cell population in many tumours and support cancer progression, metastasis and resistance to therapies through bidirectional signalling with both tumour cells and other cells within the TME. More recently, CAFs have been shown to also affect the anti-tumour immune response through direct and indirect interactions with immune cells. In this review, we specifically focus on the interactions between CAFs and cytotoxic CD8+ T cells, and on how these interactions affect T cell recruitment, infiltration and function in the tumour. We additionally provide insight into the therapeutic implications of targeting these interactions, particularly in the context of cancer immunotherapy.

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Cancer‐associated fibroblasts: Secretions, interactions, and therapy

Cited by 72 publications

References 67 publications

miR-338-3p Is Regulated by Estrogens through GPER in Breast Cancer Cells and Cancer-Associated Fibroblasts (CAFs)

miR-338-3p Is Regulated by Estrogens through GPER in Breast Cancer Cells and Cancer-Associated Fibroblasts (CAFs)

Modifying the tumour microenvironment and reverting tumour cells: New strategies for treating malignant tumours

Cancer-Associated Fibroblast Mediated Inhibition of CD8+ Cytotoxic T Cell Accumulation in Tumours: Mechanisms and Therapeutic Opportunities

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