Gastric cancer‐derived exosomes promote peritoneal metastasis by destroying the mesothelial barrier

Deng, Guang; Qu, Junle; Zhang, Ye; Che, Xiaofang; Yu, Changhong; Fan, Yibo; Zhang, Simeng; Di, Na; Liu, Yunpeng; Qu, Xiujuan

doi:10.1002/1873-3468.12722

Cited by 86 publications

(82 citation statements)

References 53 publications

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“…Exosomes have been reported to play important roles in gastric cancer and have the potential to be used as ideal biomarkers for gastric cancer diagnosis, prognosis and therapy. Gastric cancer derived exosomes facilitate peritoneal metastasis by disrupting mesothelial barrier and inducing peritoneal fibrosis . Exosomes secreted from gastric cancer cells deliver EGFR to regulate liver microenvironment, promoting gastric cancer liver metastasis .…”

Section: Introductionmentioning

confidence: 99%

Exosomal miR‐423‐5p targets SUFU to promote cancer growth and metastasis and serves as a novel marker for gastric cancer

Yang

Wang

et al. 2018

Molecular Carcinogenesis

128

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Exosomes are critically involved in tumor growth, metastasis, and therapy resistance. Exosomes have the potential to be utilized as cancer biomarkers. In this study, we aimed to explore the roles and clinical values of exosomal miRNAs in gastric cancer. We found that the concentration of exosomes was significantly higher in the serum of gastric cancer patients and the culture supernatants of gastric cancer cells than that in healthy volunteers and gastric mucosa epithelial cells. In particular, miR-423-5p was elevated in the serum exosomes of gastric cancer patients, and the level of exosomal miR-423-5p was remarkably correlated with lymph node metastasis. High level of exosomal miR-423-5p was associated with poor outcome in gastric cancer patients. MiR-423-5p enriched exosomes could be internalized into gastric cancer cells, which enhanced cell proliferation and migration both in vitro and in vivo. Mechanistically, miR-423-5p inhibited the expression of suppressor of fused protein (SUFU) to enhance the proliferation and migration of gastric cancer cells. The expression levels of SUFU were significantly decreased in gastric cancer cells and the tumor tissues of gastric cancer patients. Taken together, our findings indicate that exosomes could deliver miR-423-5p to promote cancer growth and metastasis and serum exosomal miR-423-5p may serve as a potential marker for gastric cancer diagnosis and prognosis.

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Section: Introductionmentioning

confidence: 99%

Exosomal miR‐423‐5p targets SUFU to promote cancer growth and metastasis and serves as a novel marker for gastric cancer

Yang

Wang

et al. 2018

Molecular Carcinogenesis

128

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“…Exosomes containing active proteases are able to induce ECM degradation, and they contribute to ECM remodeling by selectively or directly binding to the ECM‐binding motif presented on exosomal surface adhesion proteins, which enhances fibroblast adhesion and migration . Gastric cancer‐derived exosomes facilitate peritoneal metastasis by causing mesothelial barrier disruption and peritoneal fibrosis through concurrent apoptosis and MMT . Similar to primary tumor sites, TDEs also participate in the conversion of fibroblasts to CAFs phenotype within the pre‐metastatic niche, thus facilitating cancer metastasis.…”

Section: Exosomes In Sequential Processes Of Tumor Metastasismentioning

confidence: 99%

“…97 Gastric cancer-derived exosomes facilitate peritoneal metastasis by causing mesothelial barrier disruption and peritoneal fibrosis through concurrent apoptosis and MMT. 98 Similar to primary tumor sites, TDEs also participate in the conversion of fibroblasts to CAFs phenotype within the pre-metastatic niche, thus facilitating cancer metastasis. In HCC, highmetastatic cells secrete exosomal miR-1247-3p that directly targets B4GALT3, leading to activation of β1-integrin-NF-κB signaling in fibroblasts.…”

Section: Exosomal Integrin Model Only Until 2015 Hoshino Et Almentioning

confidence: 99%

Exosomes play roles in sequential processes of tumor metastasis

Chen

et al. 2018

Intl Journal of Cancer

141

105

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Overwhelming evidence demonstrates that exosomes, a series of biologically functional small vesicles of endocytic origin carrying a variety of active constituents, especially tumor-derived exosomes, contribute to tumor progression and metastasis. This review focuses on the specific multifaceted roles of exosomes in affecting sequenced four crucial processes of metastasis, through which cancer cells spread from primary to secondary organs and finally form macroscopic metastatic lesions. First, exosomes modulate the primary tumor sites to assist cancer growth and dissemination. In this part, five main biological events are reviewed, including the transfer of oncogenic constituents, the recruitment and activation of fibroblasts, the induction of angiogenesis, immunosuppression and epithelial-mesenchymal transition (EMT) promotion. In Step 2, we list two recently disclosed mechanisms during the organ-specific homing process: the exosomal integrin model and exosomal epidermal growth factor receptor (EGFR)/miR-26/hepatocyte growth factor (HGF) model. Subsequently, Step 3 focuses on the interactions between exosomes and pre-metastatic niche, in which we highlight the specific functions of exosomes in angiogenesis, lymphangiogenesis, immune modulation and metabolic, epigenetic and stromal reprogramming of pre-metastatic niche. Finally, we summarize the mechanisms of exosomes in helping the metastatic circulating tumor cells escape from immunologic surveillance, survive in the blood circulation and proliferate in host organs.

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“…Deng et al (38) pretreated nude mice with MGC803 cell-derived exosomes and injected MGC803 cells into the abdominal cavity, and observed that the total weight of the tumor nodules was significantly increased compared with in PBS-treated mice in vivo. Mesothelial cells (HMrSV5) were also cultured with exosomes, which revealed that exosomes induced injury of peritoneal mesothelial cells by promoting apoptosis and MMT, via upregulation of the extracellular signal-regulated kinase pathway (38).…”

Section: Exosomes In Peritoneal Dissemination Of Gastric Cancermentioning

confidence: 99%

“…Mesothelial cells (HMrSV5) were also cultured with exosomes, which revealed that exosomes induced injury of peritoneal mesothelial cells by promoting apoptosis and MMT, via upregulation of the extracellular signal-regulated kinase pathway (38).…”

Section: Exosomes In Peritoneal Dissemination Of Gastric Cancermentioning

confidence: 99%

Exosome‑mediated peritoneal dissemination in gastric cancer and its clinical applications (Review)

Chen

Jin

et al. 2018

biom rep

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Abstract. The prognosis of patients with peritoneal dissemination from gastric cancer is poor, and the underlying molecular mechanism remains unclear. Exosomes, as macromolecular phospholipid bilayer vesicles comprising of proteins, nucleic acids and lipids, serve as mediators of cell-cell communication. Gastric cancer tumor-derived exosomes may be involved in the pathological process of peritoneal dissemination by mediating crosstalk between cancer cells and mesothelial cells, to result in the induction of enhanced tumor growth, migratory, adhesive and invasive abilities, peritoneal fibrosis and apoptosis, mesothelial-to-mesenchymal transition, angiogenesis and chemoresistance. The present review focuses on previous studies addressing the exosome-dependent molecular transfer in peritoneal dissemination in gastric cancer and the potential clinical applications. Contents1. Introduction 2. Exosomes in peritoneal dissemination of gastric cancer 3. Early detection by exosomal miRNAs 4. Chemoresistance and exosome-based treatment of peritoneal dissemination cases of gastric cancer IntroductionPeritoneal dissemination is detected in 14% of patients with gastric cancer at the time of initial diagnosis, for whom the median survival time is 4 months (1). Gastric cancer patients with peritoneal dissemination cannot undergo radical surgery, and the chemotherapeutic effect is limited due to inadequate distribution of intravenous chemotherapy drugs, blocked by the peritoneal barrier, and tumor chemoresistance (2). The 5-year survival rate of gastric cancer patients with peritoneal dissemination is only 2% (3). Peritoneal dissemination is among the most common patterns of recurrence in gastric cancer patients (4). However, it remains unclear how peritoneal dissemination exactly occurs, and there is a need to reveal the underlying molecular mechanism, as well as to develop more effective treatment strategies. Exosomes are macromolecular, phospholipid bilayer vesicles comprised of proteins, nucleic acids and lipids (5). At 40-120 nm in diameter, exosomes are smaller than other vesicles including microvesicles (100 nm-1 µm) and apoptotic bodies (50 nm-2 µm) (6). Exosomes exist in all body fluids and are generated by secretion and budding from various types of cells, including tumor cells (7). They contain key biological molecules including proteins, RNAs and lipids, which are considered to mediate intercellular communication (6). In particular, exosomes deliver proteins and RNAs associated with different pathologies, including neurodegenerative diseases, HIV infection, heart disease and tumor progression, from host cells to recipient cells (8). Tumor-derived exosomes (TEX) may have the capacity to remodel the tumor microenvironment to make it favorable for metastatic niches (7) and, furthermore, may alter the extracellular matrix and attract more cancer cells to the niches (9). Notably, increasing studies indicate that exosomes are involved in the peritoneal dissemination of gastric cancer. The present review focuses on how exos...

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Gastric cancer‐derived exosomes promote peritoneal metastasis by destroying the mesothelial barrier

Cited by 86 publications

References 53 publications

Exosomal miR‐423‐5p targets SUFU to promote cancer growth and metastasis and serves as a novel marker for gastric cancer

Exosomal miR‐423‐5p targets SUFU to promote cancer growth and metastasis and serves as a novel marker for gastric cancer

Exosomes play roles in sequential processes of tumor metastasis

Exosome‑mediated peritoneal dissemination in gastric cancer and its clinical applications (Review)

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