Cancer-associated fibroblasts suppress ferroptosis and induce gemcitabine resistance in pancreatic cancer cells by secreting exosome-derived ACSL4-targeting miRNAs

Qi, Ran; Bai, Yu‐Jun; Li, Kun; Liu, Nanbin; Xu, Yan; Dal, Emre; Wang, Yufeng; Lin, Rui; Wang, Hui; Liu, Zhongyan; Li, Xinbo; Wang, Xiuyan; Shi, Baomin

doi:10.1016/j.drup.2023.100960

Cited by 99 publications

(31 citation statements)

References 50 publications

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“…The role of exosomes in tumor‐stroma crosstalk is another critical area of research. CAFs could communicate with cancer cells via exosomes, contributing to chemotherapy resistance 35–37 . Tumor‐derived exosomes could reprogram fibroblasts into CAFs, subsequently promoting tumor growth 38–40 .…”

Section: Overview Of Exosomes and Tumor‐stroma Cross Talk In Crcmentioning

confidence: 99%

“…CAFs could communicate with cancer cells via exosomes, contributing to chemotherapy resistance. [35][36][37] Tumor-derived exosomes could reprogram fibroblasts into CAFs, subsequently promoting tumor growth. [38][39][40] Exosomes have also been shown to play a crucial role in modulating the tumor metabolic microenvironment.…”

Section: Exosomes As Messengers In Tumor-stroma Crosstalkmentioning

confidence: 99%

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Exosomes in tumor‐stroma crosstalk: Shaping the immune microenvironment in colorectal cancer

Zhang,

Huo,

et al. 2024

The FASEB Journal

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Colorectal cancer (CRC) is a multifaceted disease characterized by a complex interaction between tumor cells and the surrounding microenvironment. Within this intricate landscape, exosomes have emerged as pivotal players in the tumor‐stroma crosstalk, influencing the immune microenvironment of CRC. These nano‐sized vesicles, secreted by both tumoral and stromal cells, serve as molecular transporters, delivering a heterogeneous mix of biomolecules such as RNAs, proteins, and lipids. In the CRC context, exosomes exert dual roles: they promote tumor growth, metastasis, and immune escape by altering immune cell functions and activating oncogenic signaling pathways and offer potential as biomarkers for early CRC detection and treatment targets. This review delves into the multifunctional roles of exosomes in the CRC immune microenvironment, highlighting their potential implications for future therapeutic strategies and clinical outcomes.

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Section: Overview Of Exosomes and Tumor‐stroma Cross Talk In Crcmentioning

confidence: 99%

Section: Exosomes As Messengers In Tumor-stroma Crosstalkmentioning

confidence: 99%

Exosomes in tumor‐stroma crosstalk: Shaping the immune microenvironment in colorectal cancer

Zhang,

Huo,

et al. 2024

The FASEB Journal

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“…97 Exosomes derived from CAFs in pancreatic cancer can suppress ferroptosis as well as induce resistance to gemcitabine through exosome-derived miRNAs targeting acyl-CoA synthetase long-chain family member 4 (ACSL4). The chemoresistance after gemcitabine therapy is achieved by CAF exosome-derived miR-3173-5p, which sponges ACSL4 and is taken up by cancer cells postinhibition of ferroptosis 98 37003125. In a study of nasopharyngeal carcinoma, whose treatment failure is mainly caused by metastasis, macrophage migration inhibitory factor (MIF) was increased in nasopharyngeal carcinoma cells, whereas the nasopharyngeal carcinoma cells secret exosomes that could be absorbed by macrophages, to inhibit the macrophage ferroptosis and promote the nasopharyngeal carcinoma metastasis.…”

Section: Ferroptosismentioning

confidence: 99%

The role of exosomes in cancer‐related programmed cell death

Li,

Jing,

et al. 2023

Immunological Reviews

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SummaryCancer arises from the growth and division of uncontrolled erroneous cells. Programmed cell death (PCD), or regulated cell death (RCD), includes natural processes that eliminate damaged or abnormal cells. Dysregulation of PCD is a hallmark of cancer, as cancer cells often evade cell death and continue to proliferate. Exosomes nanoscale extracellular vesicles secreted by different types of cells carrying a variety of molecules, including nucleic acids, proteins, and lipids, to have indispensable role in the communication between cells, and can influence various cellular processes, including PCD. Exosomes have been shown to modulate PCD in cancer cells by transferring pro‐ or antideath molecules to neighboring cells. Additionally, exosomes can facilitate the spread of PCD to surrounding cancer cells, making them promising in the treatment of various cancers. The exosomes' diagnostic potential in cancer is also an active area of research. Exosomes can be isolated from a wide range of bodily fluids and tissues, such as blood and urine, and can provide a noninvasive way to monitor cancer progression and treatment response. Furthermore, exosomes have also been employed as a delivery system for therapeutic agents. By engineering exosomes to carry drugs or other therapeutic molecules, they can be targeted specifically to cancer cells, reducing toxicity to healthy tissues. Here, we discussed exosomes in the diagnosis and prevention of cancers, tumor immunotherapy, and drug delivery, as well as in different types of PCD.

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“…Nuclear Nrf2 enhanced the expression of its target genes HO‐1 and NAD(P)H quinone dehydrogenase 1 (NQO1), thereby reducing the sensitivity of GBM cells to temozolomide by inhibiting ferroptosis. Qi et al demonstrated that cancer‐associated fibroblasts secreted exosomes containing high levels of miR‐3173–5p during gemcitabine chemotherapy (Qi et al, 2023). Importantly, these exosomes could block ferroptosis in pancreatic cancer cells by inhibiting the expression of ACSL4 and thus lead to gemcitabine resistance.…”

Section: Multifaceted Roles Of Ferroptosis In Cancermentioning

confidence: 99%

Ferroptosis: Potential opportunities for natural products in cancer therapy

Nie,

Shen,

Zhou

et al. 2023

Phytotherapy Research

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Cancer cells often exhibit defects in the execution of cell death, resulting in poor clinical outcomes for patients with many cancer types. Ferroptosis is a newly discovered form of programmed cell death characterized by intracellular iron overload and lipid peroxidation in the cell membrane. Increasing evidence suggests that ferroptosis is closely associated with a wide variety of physiological and pathological processes, particularly in cancer. Notably, various bioactive natural products have been shown to induce the initiation and execution of ferroptosis in cancer cells, thereby exerting anticancer effects. In this review, we summarize the core regulatory mechanisms of ferroptosis and the multifaceted roles of ferroptosis in cancer. Importantly, we focus on natural products that regulate ferroptosis in cancer cells, such as terpenoids, polyphenols, alkaloids, steroids, quinones, and polysaccharides. The clinical efficacy, adverse effects, and drug–drug interactions of these natural products need to be evaluated in further high‐quality studies to accelerate their application in cancer treatment.

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Cancer-associated fibroblasts suppress ferroptosis and induce gemcitabine resistance in pancreatic cancer cells by secreting exosome-derived ACSL4-targeting miRNAs

Cited by 99 publications

References 50 publications

Exosomes in tumor‐stroma crosstalk: Shaping the immune microenvironment in colorectal cancer

Exosomes in tumor‐stroma crosstalk: Shaping the immune microenvironment in colorectal cancer

The role of exosomes in cancer‐related programmed cell death

Ferroptosis: Potential opportunities for natural products in cancer therapy

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