Diversity and Biology of Cancer-Associated Fibroblasts

Physiological Reviews, Journal Year: 2020, Volume and Issue: 101(1), P. 147 - 176

Published: May 29, 2020

Efforts to develop anti-cancer therapies have largely focused on targeting the epithelial compartment, despite presence of non-neoplastic stromal components that substantially contribute progression tumor. Indeed, cancer cell survival, growth, migration, and even dormancy are influenced by surrounding tumor microenvironment (TME). Within TME, cancer-associated fibroblasts (CAFs) been shown play several roles in development a They secrete growth factors, inflammatory ligands, extracellular matrix proteins promote proliferation, therapy resistance, immune exclusion. However, recent work indicates CAFs may also restrain some circumstances. In this review, we summarize body CAFs, with particular focus most discoveries about fibroblast heterogeneity, plasticity, functions. We highlight commonalities present across different types, normal states. Finally, latest advances regarding therapeutic strategies undergoing preclinical clinical evaluation.

Language: Английский

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Signaling pathways in cancer-associated fibroblasts and targeted therapy for cancer

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: June 10, 2021

Abstract To flourish, cancers greatly depend on their surrounding tumor microenvironment (TME), and cancer-associated fibroblasts (CAFs) in TME are critical for cancer occurrence progression because of versatile roles extracellular matrix remodeling, maintenance stemness, blood vessel formation, modulation metabolism, immune response, promotion cell proliferation, migration, invasion, therapeutic resistance. CAFs highly heterogeneous stromal cells crosstalk with is mediated by a complex intricate signaling network consisting transforming growth factor-beta, phosphoinositide 3-kinase/AKT/mammalian target rapamycin, mitogen-activated protein kinase, Wnt, Janus kinase/signal transducers activators transcription, epidermal factor receptor, Hippo, nuclear kappa-light-chain-enhancer activated B cells, etc., pathways. These signals exhibit own special characteristics during the have potential to be targeted anticancer therapy. Therefore, comprehensive understanding these cascades interactions between necessary fully realize pivotal cancers. Herein, this review, we will summarize enormous amounts findings mediating its related targets or trials. Further, hypothesize three targeting strategies, including, namely, epithelial–mesenchymal common targets, sequential perturbation, crosstalk-directed paving way CAF-directed host cell-directed antitumor

Language: Английский

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Isolation and characterization of exosomes for cancer research

Journal of Hematology & Oncology, Journal Year: 2020, Volume and Issue: 13(1)

Published: Nov. 10, 2020

Abstract Exosomes are a subset of extracellular vesicles that carry specific combinations proteins, nucleic acids, metabolites, and lipids. Mounting evidence suggests exosomes participate in intercellular communication act as important molecular vehicles the regulation numerous physiological pathological processes, including cancer development. released by various cell types under both normal conditions, they can be found multiple bodily fluids. Moreover, carrying wide variety macromolecules provide window into altered cellular or tissue states. Their presence biological fluids renders them an attractive, minimally invasive approach for liquid biopsies with potential biomarkers diagnosis, prediction, surveillance. Due to their biocompatibility low immunogenicity cytotoxicity, have clinical applications development innovative therapeutic approaches. Here, we summarize recent advances technologies exosome isolation research. We outline functions regulating tumor metastasis, drug resistance, immune modulation context Finally, discuss prospects challenges exosome-based therapeutics.

Language: Английский

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Exosomal long noncoding RNA LNMAT2 promotes lymphatic metastasis in bladder cancer

Journal of Clinical Investigation, Journal Year: 2019, Volume and Issue: 130(1), P. 404 - 421

Published: Oct. 8, 2019

Patients with bladder cancer (BCa) clinical lymph node (LN) metastasis have an extremely poor prognosis. VEGF-C has been demonstrated to play vital roles in LN BCa. However, approximately 20% of BCa exhibits low expression, suggesting a VEGF-C–independent mechanism for Herein, we demonstrate that cell–secreted exosome-mediated lymphangiogenesis promoted manner. We identified exosomal long noncoding RNA (lncRNA), termed metastasis-associated transcript 2 (LNMAT2), stimulated human lymphatic endothelial cell (HLEC) tube formation and migration vitro enhanced tumor vivo. Mechanistically, LNMAT2 was loaded exosomes by directly interacting heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1). Subsequently, internalized HLECs epigenetically upregulated prospero homeobox 1 (PROX1) expression recruitment hnRNPA2B1 increasing the H3K4 trimethylation level PROX1 promoter, ultimately resulting metastasis. Therefore, our findings highlight lncRNA-mediated identify as therapeutic target

Language: Английский

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Roles and mechanisms of exosomal non-coding RNAs in human health and diseases

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: Nov. 10, 2021

Exosomes play a role as mediators of cell-to-cell communication, thus exhibiting pleiotropic activities to homeostasis regulation. Exosomal non-coding RNAs (ncRNAs), mainly microRNAs (miRNAs), long (lncRNAs), and circular (circRNAs), are closely related variety biological functional aspects human health. When the exosomal ncRNAs undergo tissue-specific changes due diverse internal or external disorders, they can cause tissue dysfunction, aging, diseases. In this review, we comprehensively discuss underlying regulatory mechanisms exosomes in addition, explore current knowledge on roles miRNAs, lncRNAs, circRNAs health diseases, including cancers, metabolic neurodegenerative cardiovascular autoimmune infectious determine their potential implication biomarker identification therapeutic exploration.

Language: Английский

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CAF Subpopulations: A New Reservoir of Stromal Targets in Pancreatic Cancer

Trends in cancer, Journal Year: 2019, Volume and Issue: 5(11), P. 724 - 741

Published: Oct. 21, 2019

Cancer-associated fibroblasts (CAFs) are one of the most significant components in tumour microenvironment (TME), where they can perform several protumourigenic functions. Several studies have recently reported that CAFs more heterogenous and plastic than was previously thought. As such, there has been a shift field to study CAF subpopulations emergent functions these subsets tumourigenesis. In this review, we explore how different aspects heterogeneity defined manifest multiple cancers, with focus on pancreatic ductal adenocarcinoma (PDAC). We also discuss therapeutic approaches selectively target functions, while avoiding normal fibroblasts, providing insight into future stromal targeting for treatment PDAC other solid tumours.

Language: Английский

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Extracellular vesicles in the tumor microenvironment: old stories, but new tales

Molecular Cancer, Journal Year: 2019, Volume and Issue: 18(1)

Published: March 30, 2019

Mammalian cells synthesize and release heterogeneous extracellular vesicles (EVs) which can be generally recognized as subclasses including exosomes, microvesicles (MVs), apoptotic bodies (ABs), each differing in their biogenesis, composition biological functions from others. EVs originate normal or cancer cells, transfer bioactive cargoes to both adjacent distant sites, orchestrate multiple key pathophysiological events such carcinogenesis malignant progression. Emerging messengers that mediate intercellular communications, are being paid substantial attention various disciplines but not limited biology immunology. Increasing lines of research advances have revealed the critical role establishment maintenance tumor microenvironment (TME), sustaining cell proliferation, evading growth suppression, resisting death, acquiring genomic instability reprogramming stromal lineages, together contributing generation a functionally remodeled TME. In this article, we present updates on major topics document how implicated proliferative expansion promotion drug resistance, metabolic activity, enhancement metastatic potential, induction angiogenesis, escape immune surveillance. Appropriate insightful understanding contribution progression lead new avenues prevention, diagnosis treatment human malignancies future medicine.

Language: Английский

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Apoptosis Deregulation and the Development of Cancer Multi-Drug Resistance

Cancers, Journal Year: 2021, Volume and Issue: 13(17), P. 4363 - 4363

Published: Aug. 28, 2021

The ability of tumor cells to evade apoptosis is established as one the hallmarks cancer. deregulation apoptotic pathways conveys a survival advantage enabling cancer develop multi-drug resistance (MDR), complex phenotype referring concurrent toward agents with different function and/or structure. Proteins implicated in intrinsic pathway apoptosis, including Bcl-2 superfamily and Inhibitors Apoptosis (IAP) family members, well their regulator, suppressor p53, have been development MDR many types. PI3K/AKT pivotal promoting proliferation often overactive tumors. In addition, microenvironment, particularly factors secreted by cancer-associated fibroblasts, can inhibit reduce effectiveness anti-cancer drugs. this review, we describe main alterations that occur apoptosis-and related promote MDR. We also summarize therapeutic approaches against resistant tumors, targeting small molecule inhibitors IAPs or AKT natural origin may be used monotherapy combination conventional therapeutics. Finally, highlight potential exploitation epigenetic modifications reverse phenotype.

Language: Английский

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Cancer associated-fibroblast-derived exosomes in cancer progression

Molecular Cancer, Journal Year: 2021, Volume and Issue: 20(1)

Published: Dec. 1, 2021

To identify novel cancer therapies, the tumor microenvironment (TME) has received a lot of attention in recent years particular with advent clinical successes achieved by targeting immune checkpoint inhibitors (ICIs). The TME consists multiple cell types that are embedded extracellular matrix (ECM), including cells, endothelial cells and associated fibroblasts (CAFs), which communicate each other during progression. CAFs dominant heterogeneous type within pivotal role controlling invasion metastasis, evasion, angiogenesis chemotherapy resistance. mediate their effects part remodeling ECM secreting soluble factors vesicles. Exosomes subtype vesicles (EVs), contain various biomolecules such as nucleic acids, lipids, proteins. exosomes can be transmitted from one to another cell, thereby affect behavior receiving cell. As also present circulation, contents explored biomarkers for diagnosis prognosis patients. In this review, we concentrate on CAFs-derived communication between TME. First, introduce roles tumorigenesis. Thereafter, discuss ways interplay TME, focus exosomes. Then, elaborate mechanisms contribute progression, well impact We conclude discussing aspects deserve further investigation, emerging insights into making treatment inhibitor blockade more efficient.

Language: Английский

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Exosome biogenesis, secretion and function of exosomal miRNAs in skeletal muscle myogenesis

Cell Proliferation, Journal Year: 2020, Volume and Issue: 53(7)

Published: June 24, 2020

Exosomes are membrane-bound extracellular vesicles that produced in the endosomal compartment of most mammalian cell types and then released. effective carriers for intercellular material transfer can influence a series physiological pathological processes recipient cells. Among loaded cargoes, non-coding RNAs (ncRNAs) vary exosome-producing its homeostatic state, characterization biogenesis secretion exosomal ncRNAs functions these skeletal muscle myogenesis remain preliminary. In this review, we will describe what is currently known exosome biogenesis, release uptake ncRNAs, as well varied miRNAs myogenesis.

Language: Английский

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