Exosomes derived from cancer-associated fibroblasts mediate response to cancer therapy

Masoudi-Khoram, Nastaran; Soheilifar, Mohammad Hasan; Ghorbanifar, Shima; Nobari, Sima; Hakimi, Maryam; Hassani, Mahmoud

doi:10.1016/j.critrevonc.2023.103967

Cited by 15 publications

(8 citation statements)

References 111 publications

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“…Our in vitro cell experiments found that HP‐TAF‐EVs could transmit H19 into MCF‐7 cells, in which H19 promoted cell growth, metastasis, and TAX resistance. Indeed, lncRNAs contained in EVs can be transferred between cells within the tumor microenvironment and alter the behaviors of recipient cells, contributing to resistance to chemotherapy and radiotherapy 46 . Previous studies have confirmed the malignant tumor progression of H19; H19 can induce autophagy in BC cells through the SAHH/DNMT3B signaling axis to promote TAX resistance 47 .…”

Section: Discussionmentioning

confidence: 99%

Extracellular vesicles released by hypoxia‐induced tumor‐associated fibroblasts impart chemoresistance to breast cancer cells via long noncoding RNA H19 delivery

Tao,

Wang,

et al. 2024

The FASEB Journal

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Recently, extracellular vesicles (EVs) have been emphasized in regulating the hypoxic tumor microenvironment of breast cancer (BC), where tumor‐associated fibroblasts (TAFs) play a significant role. In this study, we describe possible molecular mechanisms behind the pro‐tumoral effects of EVs, secreted by hypoxia (HP)‐induced TAFs, on BC cell growth, metastasis, and chemoresistance. These mechanisms are based on long noncoding RNA H19 (H19) identified by microarray analysis. We employed an in silico approach to identify differentially expressed lncRNAs that were associated with BC. Subsequently, we explored possible downstream regulatory mechanisms. We isolated EVs from TAFs that were exposed to HP, and these EVs were denoted as HP‐TAF‐EVs henceforth. MTT, transwell, flow cytometry, and TUNEL assays were performed to assess the malignant phenotypes of BC cells. A paclitaxel (TAX)‐resistant BC cell line was constructed, and xenograft tumor and lung metastasis models were established in nude mice for in vivo verification. Our observation revealed that lncRNA H19 was significantly overexpressed, whereas miR‐497 was notably downregulated in BC. HP induced activation of TAFs and stimulated the secretion of EVs. Coculture of HP‐TAF‐EVs and BC cells led to an increase in TAX resistance of the latter. HP‐TAF‐EVs upregulated methylation of miR‐497 by delivering lncRNA H19, which recruited DNMT1, thus lowering the expression of miR‐497. In addition, lncRNA H19‐containing HP‐TAF‐EVs hindered miR‐497 expression, enhancing tumorigenesis and TAX resistance of BC cells in vivo. Our study presents evidence for the contribution of lncRNA H19‐containing HP‐TAF‐EVs in the reduction of miR‐497 expression through the recruitment of DNMT1, which in turn promotes the growth, metastasis, and chemoresistance of BC cells.

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Section: Discussionmentioning

confidence: 99%

Extracellular vesicles released by hypoxia‐induced tumor‐associated fibroblasts impart chemoresistance to breast cancer cells via long noncoding RNA H19 delivery

Tao,

Wang,

et al. 2024

The FASEB Journal

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“…Tumor microenvironment (TME): a vascularized stroma containing a complex network of normal (non-neoplastic) and neoplastic cells. The primary constituents of the TME are cancer-associated fibroblasts (CAFs), one of the many stromal cell types 8 . Pancreatic cancer is a malignant tumor with a poor blood supply that occupies more than 90% of the tumor volume 21 .…”

Section: Discussionmentioning

confidence: 99%

“…Tumor cells and CAFs communicate in a variety of ways. It has been found that CAFs can aid cancer cells in acquiring energy, synthetic products, and a suitable environment to help cancer tissue adaptability, posing a challenge to anticancer therapy 7 , 8 .…”

Section: Introductionmentioning

confidence: 99%

NNT-AS1 in CAFs-derived exosomes promotes progression and glucose metabolism through miR-889-3p/HIF-1α in pancreatic adenocarcinoma

Zhang,

Wang,

et al. 2024

Sci Rep

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It is metabolic and signaling crosstalk between stromal cells and tumors in the tumor microenvironment, which influences several aspects of tumor formation and drug resistance, including metabolic reprogramming. Despite considerable findings linking lncRNAs in HIF-1-related regulatory networks to cancer cell, little emphasis has been given to the role in communication between cancer-associated fibroblasts (CAFs) and tumor cells. Previously, we observed that NNT-AS1 was substantially expressed in CAFs cells and CAFs exosomes, and subsequently investigated the influence of CAFs exosomal NNT-AS1 on glucose metabolism, proliferation, and metastasis of pancreatic ductal adenocarcinoma (PDAC) cells. Transmission electron microscopy was used to examine exosomes secreted by PDAC patient-derived CAFs. qRT-PCR was used to evaluate the expression of NNT-AS1, miR-889-3p, and HIF-1. The role of CAFs-derived exosomal NNT-AS1 in PDAC cell progression and metabolism have been identified. Dual luciferase reporter assays examined the binding between NNT-AS1, miR-889-3p, and HIF-1. After PDAC cells co-culture exosomes secreted by CAFs, we found that they alter glucose metabolism, proliferation, and metastasis. In PDAC cells, CAF-derived exosomal lncRNA NNT-AS1 acted as a molecular sponge for miR-889-3p. Furthermore, HIF-1 could be targeted by miR-889-3p and was controlled by NNT-AS1. This study explores the mechanism by which NNT-AS1 influences the interaction of CAFs on glycolytic remodeling, proliferation, and metastasis of tumor cells through regulating miR-889-3p/HIF-1α, which also helps discover new clinical treatment targets for PDAC.

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“…It has long been recognized that CAFs exhibit many malignant properties when compared with NFs. Numerous publications have shown that pro-tumorigenic factors secreted by CAFs can be transferred into tumor cells through the paracrine signaling [ 41 , 42 ] and the exosome-mediated pathway [ 43 , 44 ], which facilitates cancer cell stemness, proliferation, and migration. As confirmed by in vitro and in vivo experiments, CAFs also stimulate tumor angiogenesis by secreting pro-angiogenic factors, such as VEGFA, CXCL12, FGF2, and PDGFC [ 45 ].…”

Section: The Properties Of Cafsmentioning

confidence: 99%

Crosstalk between cancer-associated fibroblasts and regulated cell death in tumors: insights into apoptosis, autophagy, ferroptosis, and pyroptosis

Chen,

Liu,

Lin

et al. 2024

Cell Death Discov.

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Cancer-associated fibroblasts (CAFs), the main stromal component of the tumor microenvironment (TME), play multifaceted roles in cancer progression through paracrine signaling, exosome transfer, and cell interactions. Attractively, recent evidence indicates that CAFs can modulate various forms of regulated cell death (RCD) in adjacent tumor cells, thus involving cancer proliferation, therapy resistance, and immune exclusion. Here, we present a brief introduction to CAFs and basic knowledge of RCD, including apoptosis, autophagy, ferroptosis, and pyroptosis. In addition, we further summarize the different types of RCD in tumors that are mediated by CAFs, as well as the effects of these modes of RCD on CAFs. This review will deepen our understanding of the interactions between CAFs and RCD and might offer novel therapeutic avenues for future cancer treatments.

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Exosomes derived from cancer-associated fibroblasts mediate response to cancer therapy

Cited by 15 publications

References 111 publications

Extracellular vesicles released by hypoxia‐induced tumor‐associated fibroblasts impart chemoresistance to breast cancer cells via long noncoding RNA H19 delivery

Extracellular vesicles released by hypoxia‐induced tumor‐associated fibroblasts impart chemoresistance to breast cancer cells via long noncoding RNA H19 delivery

NNT-AS1 in CAFs-derived exosomes promotes progression and glucose metabolism through miR-889-3p/HIF-1α in pancreatic adenocarcinoma

Crosstalk between cancer-associated fibroblasts and regulated cell death in tumors: insights into apoptosis, autophagy, ferroptosis, and pyroptosis

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