Role of Exosomes in Crosstalk Between Cancer-Associated Fibroblasts and Cancer Cells

Yang, Xi; Li, Yida; Zou, Liang; Zhu, Zhengfei

doi:10.3389/fonc.2019.00356

Cited by 138 publications

(133 citation statements)

References 64 publications

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“…CAFs are the main stromal cells in the TME and aggravate tumor progression. Increasing studies have highlighted the important role of exosomes in crosstalk between CAFs and cancer cells via carrying miRNAs, lncRNAs, proteins, metabolites, and other substances . For example, Sun et al found that CAFs exosome promoted oral squamous cell carcinoma (OSCC) cell migration and invasion by transporting miR‐382‐5p to OSCC cells .…”

Section: Discussionmentioning

confidence: 99%

Cancer‐associated fibroblasts–derived exosomes‐mediated transfer of LINC00355 regulates bladder cancer cell proliferation and invasion

Yan

Wang

Fang

et al. 2019

Cell Biochemistry & Function

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The aim of this study was to investigate the regulatory mechanism of cancerassociated fibroblasts (CAFs) exosome in bladder cancer (BC) cell proliferation and invasion. CAFs and normal fibroblasts (NFs) were isolated from tumor tissues and adjacent normal tissues of BC patients, and examined by immunocytochemistry for the expression of fibroblast activation protein alpha (FAP) and α-smooth muscle actin (α-SMA). Exosomes were extracted from CAFs and NFs and observed under a transmission electron microscope, and expression of the exosome markers CD9 and CD63 was confirmed by western blotting. The distribution and intensity of fluorescence were observed by confocal laser microscopy to analyze exosomes uptake by BC cell lines T24 or 5367. BC cell proliferation and invasion were detected by MTT and Transwell assays, respectively. LINC00355 levels in CAFs, NFs, CAFs exosome, NFs exosome, and BC cells were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Results showed that CAFs exosome significantly promoted BC cell proliferation and invasion relative to NFs exosome. LINC00355 expression was significantly elevated in CAFs exosome when compared with that in NFs-exosome. Up-regulated LINC00355 expression was observed both in T24 and 5367 cells co-incubated with CAFs exosome. Exosomes derived from LINC00355 siRNA-transfected CAFs observably repressed BC cell proliferation and invasion when compared with control siRNA-CAFs exosome. In conclusion, CAFs exosome-mediated transfer of LINC00355 regulates BC cell proliferation and invasion. Significance of the study. In this study, our data suggest that the exosomes released from CAFs promote BC cell proliferation and invasion.The mechanism of this effect is, at least in part, related to the increased LINC00355. Regulation of LINC00355 expression in exosomes released from CAFs might be a putative therapeutic strategy against the pathogenesis of BC. K E Y W O R D Sbladder cancer, cancer associated fibroblasts, exosome, LINC00355

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Section: Discussionmentioning

confidence: 99%

Cancer‐associated fibroblasts–derived exosomes‐mediated transfer of LINC00355 regulates bladder cancer cell proliferation and invasion

Yan

Wang

Fang

et al. 2019

Cell Biochemistry & Function

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“…A role for microRNA (miRNA) in the epigenetic regulation of fibroblasts has also been reported, with distinct miRNAs activating fibroblasts in different organs.117-121 miRNAs also play a role in regulating EMT, EndMT, and macrophage-to-mesenchymal transition.122-124 Extracellular vesicles or exosome carriers of miRNA may also modulate the activation of fibroblasts in solid tumors and fibrosis (reviewed in 4,125,126). Further studies of epigenetic signatures in fibroblast subpopulations and their activation status may highlight the emergence of heterogeneity and function in disease, and possibly reveal new novel therapeutic targets.…”

Section: Epigenetic Control Of Fibroblast Identit Ymentioning

confidence: 99%

Origin and functional heterogeneity of fibroblasts

2020

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The inherent plasticity and resiliency of fibroblasts make this cell type a conventional tool for basic research. But where do they come from, are all fibroblasts the same, and how do they function in disease? The first fibroblast lineages in mammalian development emerge from the ooze of primary mesenchyme during gastrulation. They are cells that efficiently create and negotiate the extracellular matrix of the mesoderm in order to migrate and meet their developmental fate. Mature fibroblasts in epithelial tissues live in the interstitial spaces between basement membranes that spatially delimit complex organ structures. While the function of resident fibroblasts in healthy tissues is largely conjecture, the accumulation of fibroblasts in pathologic lesions offers insight into biologic mechanisms that control their function; fibroblasts are poised to coordinate fibrogenesis in tissue injury, neoplasia, and aging. Here, we examine the developmental origin and plasticity of fibroblasts, their molecular and functional definitions, the epigenetic control underlying their identity and activation, and the evolution of their immune regulatory functions. These topics are reviewed through the lens of fate mapping using genetically engineered mouse models and from the perspective of single‐cell RNA sequencing. Recent observations suggest dynamic and heterogeneous functions for fibroblasts that underscore their complex molecular signatures and utility in injured tissues.

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“…we used western blotting assay to detect the androgen receptor (AR) expression in CAFs and found that AR was expressed in all CAFs but at a lower level than LNCaP cells (Additional le 1: Figure S1b). CAF-secreted exosomes can contribute to the progression and metastasis by transferring different types of substances in various tumours [26]. Previous study showed that inhibiting AR signalling in CAFs might promote PCa cell migration by enhanced secretion of CCL2 and CXCL8 [11], we would like to determine whether exosomes derived from CAF exposed to androgen deprivation might promote migration or invasion of PCa cells.…”

Section: Characteristics Of Cafs Isolated From Pca Patients and Isolamentioning

confidence: 99%

Loss of Exosomal miR-146a-5p from Cancer-Associated Fibroblasts After Androgen Deprivation Therapy Contributes to Prostate Cancer Metastasis

Zhao

Ding

et al. 2020

Preprint

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Background: Androgen deprivation therapy (ADT) is the backbone of therapy for advanced prostate cancer (PCa). Despite the good initial response, castration resistance and metastatic progression will inevitably occur. Cancer-associated fibroblasts (CAFs) may be implicated in promoting metastasis of PCa after ADT. Our aim is to investigate the role and mechanism of CAF-derived exosomes involving in metastasis of PCa after ADT. Methods: PCa cells were co-cultured with exosomes derived from 10 nM dihydrotestosterone (DHT)-treated (simulating the high androgen level of prostate cancer microenvironment） or ethanol (ETOH) -treated (simulating the castration level of prostate cancer microenvironment after ADT) CAFs, and their migration and invasion differences under castration condition were examined both in vitro and in vivo. The miRNA profiles of exosomes derived from DHT-treated CAFs and matched ETOH-treated CAFs were analysed via next generation sequencing. The transfer of exosomal miR-146a-5p from CAFs to PCa cells was identified by fluorescent microscopy. The function and direct target gene of exosomal miR-146a-5p in PCa cells were confirmed through Transwell assays, luciferase reporter, and western blot.Results: Compared with DHT-treated CAFs, exosomes derived from ETOH-treated CAFs dramatically increase migration and invasion of PCa cells under castration condition. MiR-146a-5p level in exosomes from ETOH-treated CAFs was significantly reduced. The loss of miR-146a-5p may strengthen the epithelial-mesenchymal transition (EMT) to accelerate cancer cells metastasis by modulating epidermal growth factor receptor (EGFR)/ERK pathway. Conclusions: CAFs-derived exosomal miR-146a-5p confers metastasis in PCa cells under ADT through the EGFR/ERK pathway and it may present a new treatment for PCa

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Role of Exosomes in Crosstalk Between Cancer-Associated Fibroblasts and Cancer Cells

Cited by 138 publications

References 64 publications

Cancer‐associated fibroblasts–derived exosomes‐mediated transfer of LINC00355 regulates bladder cancer cell proliferation and invasion

Cancer‐associated fibroblasts–derived exosomes‐mediated transfer of LINC00355 regulates bladder cancer cell proliferation and invasion

Origin and functional heterogeneity of fibroblasts

Loss of Exosomal miR-146a-5p from Cancer-Associated Fibroblasts After Androgen Deprivation Therapy Contributes to Prostate Cancer Metastasis

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