Extracellular vesicle-orchestrated crosstalk between cancer-associated fibroblasts and tumors

He, Chuanshi; Wang, Linlin; Li, Ling; Zhu, Guiquan

doi:10.1016/j.tranon.2021.101231

Cited by 17 publications

(10 citation statements)

References 99 publications

(164 reference statements)

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“…It has been acknowledged that communication networks mediated by EVs in the TME are critical in tumor development [ 52 ]. Specifically, T-EVs activate NFs to form a CAF-like phenotype and maintain a pro-TME [ 53 ].…”

Section: Discussionmentioning

confidence: 99%

Extracellular Vesicles Derived from Lung Cancer Cells Induce Transformation of Normal Fibroblasts into Lung Cancer-Associated Fibroblasts and Promote Metastasis of Lung Cancer by Delivering lncRNA HOTAIR

Zhang

Qiu

et al. 2022

Stem Cells International

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Human lung cancer (LC) cells A549/H358, normal lung epithelial cells BEAS-2B, and lung normal fibroblasts (NFs) were cultured, followed by transfection of H358 cells with HOTAIR shRNA. Extracellular vesicles (EVs) extracted from H358 cells were identified. The internalization of Dil-labeled-EVs by NFs was tested, and protein levels of cancer-associated fibroblast (CAF) surface markers, inflammatory cytokines, cell proliferation, invasion, and migration, and lncRNA HOTAIR levels were determined. A549 cells were cultured in an H358-EVs-treated conditioned medium of NFs (NFCM), followed by intravenous injection of A549 cells into nude mice. The lesions and Ki-67-positive cells in lung tissues were measured. The results showed that tumor cell-derived EVs (T-EVs) motivated the transformation of NFs into CAFs. Specifically, EVs can be internalized by NFs, and the protein levels of CAF surface markers and inflammation levels were elevated in H358-EVs-treated NFs. The proliferation, invasion, and migration of A549 cells cultured in T-EVs-treated NFCM were increased. H358-EVs carried HOTAIR into NFs and promoted the transformation of NFs into CAFs. Inhibition of HOTAIR partially reversed the promoting effect of H358-EVs on the transformation of NFs into CAFs and invasion and migration of LC cells. T-EVs promoted metastasis of LC in vivo by transforming NFs into CAFs.

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Section: Discussionmentioning

confidence: 99%

Extracellular Vesicles Derived from Lung Cancer Cells Induce Transformation of Normal Fibroblasts into Lung Cancer-Associated Fibroblasts and Promote Metastasis of Lung Cancer by Delivering lncRNA HOTAIR

Zhang

Qiu

et al. 2022

Stem Cells International

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“…Remodeling of the ECM, driven by proteolytic enzymes (such as matrix metalloproteinases) [ 2 ], by enzymes that control the modification and cross-linking of extracellular matrix proteins (such as lysyloxidases (LOX)) [ 3 ], results in increased stiffness and altered ECM composition. Tumor cells also secrete extracellular vesicles with nucleic acids, lipids and proteins, which can participate in tumor progression and behavior, including tumor environment remodeling, fibroblast activation, angiogenesis, immunomodulation or the establishment of pre-metastatic niches [ 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

The Functional Role of Extracellular Matrix Proteins in Cancer

Popova

Jücker

2022

Cancers

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The extracellular matrix (ECM) is highly dynamic as it is constantly deposited, remodeled and degraded to maintain tissue homeostasis. ECM is a major structural component of the tumor microenvironment, and cancer development and progression require its extensive reorganization. Cancerized ECM is biochemically different in its composition and is stiffer compared to normal ECM. The abnormal ECM affects cancer progression by directly promoting cell proliferation, survival, migration and differentiation. The restructured extracellular matrix and its degradation fragments (matrikines) also modulate the signaling cascades mediated by the interaction with cell-surface receptors, deregulate the stromal cell behavior and lead to emergence of an oncogenic microenvironment. Here, we summarize the current state of understanding how the composition and structure of ECM changes during cancer progression. We also describe the functional role of key proteins, especially tenascin C and fibronectin, and signaling molecules involved in the formation of the tumor microenvironment, as well as the signaling pathways that they activate in cancer cells.

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“…Cancer‐associated fibroblasts, as major components of the tumor microenvironment, regulate tumorigenesis, metastasis, drug resistance, metabolic reprogramming, and immunosuppression by interacting with tumor cells by secreting cytokines, chemokines, and EVs 5,8 . Extracellular vesicles are membrane‐encapsulated nanoparticles that contain multiple bioactive molecules, such as lipids, proteins, miRNA, and long noncoding RNA, which are involved in intercellular communication 7 .…”

Section: Discussionmentioning

confidence: 99%

Extracellular vesicle‐encapsulated microRNA‐296‐3p from cancer‐associated fibroblasts promotes ovarian cancer development through regulation of the PTEN/AKT and SOCS6/STAT3 pathways

Sun,

Ke,

Yin

et al. 2023

Cancer Science

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Cancer‐associated fibroblasts (CAFs), as important components of the tumor microenvironment, can regulate intercellular communication and tumor development by secreting extracellular vesicles (EVs). However, the role of CAF‐derived EVs in ovarian cancer has not been fully elucidated. Here, using an EV‐microRNA sequencing analysis, we reveal specific overexpression of microRNA (miR)‐296‐3p in activated CAF‐derived EVs, which can be transferred to tumor cells to regulate the malignant phenotypes of ovarian cancer cells. Moreover, overexpression of miR‐296‐3p significantly promotes the proliferation, migration, invasion, and drug resistance of ovarian cancer cells in vitro, as well as tumor growth in vivo, while its inhibition has the opposite effects. Further mechanistic studies reveal that miR‐296‐3p promotes ovarian cancer progression by directly targeting PTEN and SOCS6 and activating AKT and STAT3 signaling pathways. Importantly, increased expression of miR‐296‐3p encapsulated in plasma EVs is closely correlated with tumorigenesis and chemoresistance in patients with ovarian cancer. Our results highlight the cancer‐promoting role of CAF‐derived EVs carrying miR‐296‐3p in ovarian cancer progression for the first time, and suggest that miR‐296‐3p encapsulated in CAF‐derived EVs could be a diagnostic biomarker and therapeutic target for ovarian cancer.

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Extracellular vesicle-orchestrated crosstalk between cancer-associated fibroblasts and tumors

Abstract: Highlights EVs mediate the interaction between tumor and stromal cells in the TME. Tumors mediate CAF-like activation of stromal cells through EVs. CAF-derived EVs promote tumor proliferation, metastasis and therapeutic resistance.

Cited by 17 publications

References 99 publications

Extracellular Vesicles Derived from Lung Cancer Cells Induce Transformation of Normal Fibroblasts into Lung Cancer-Associated Fibroblasts and Promote Metastasis of Lung Cancer by Delivering lncRNA HOTAIR

Extracellular Vesicles Derived from Lung Cancer Cells Induce Transformation of Normal Fibroblasts into Lung Cancer-Associated Fibroblasts and Promote Metastasis of Lung Cancer by Delivering lncRNA HOTAIR

The Functional Role of Extracellular Matrix Proteins in Cancer

Extracellular vesicle‐encapsulated microRNA‐296‐3p from cancer‐associated fibroblasts promotes ovarian cancer development through regulation of the PTEN/AKT and SOCS6/STAT3 pathways

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