Exosomes Promote Ovarian Cancer Cell Invasion through Transfer of CD44 to Peritoneal Mesothelial Cells

Nakamura, Koji; Sawada, Kenjiro; Kinose, Yasuto; Yoshimura, Akihiko; Toda, Aska; Nakatsuka, Erika; Hashimoto, Kae; Mabuchi, Seiji; Morishige, Ken‐ichirou; Kurachi, Hirohisa; Lengyel, Ernst; Kimura, Tadashi

doi:10.1158/1541-7786.mcr-16-0191

Cited by 187 publications

(171 citation statements)

References 46 publications

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“…CD44 is upregulated in cancer stem cells, regulates adhesion and metastasis, and it is a well-known metastatic marker in exosomes (Senbanjo & Chellaiah, 2017). It was found to be delivered from ovarian cancer cells to mesothelial cells where it upregulates degradation of the ECM by inducing gene expression of MMPs to promote cancer cell invasion (Nakamura et al, 2017). A specific involvement of changes in the miRNA profile, either induced by CD44 or due to RNA transported by exosomes was not noted.…”

Section: Exosomes In Cancer: Target Tissue Biohacking and Hijacking Omentioning

confidence: 99%

Ceramide and Exosomes: A Novel Target in Cancer Biology and Therapy

Elsherbini

Bieberich

2018

Advances in Cancer Research

114

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Exosomes are secreted extracellular vesicles (EVs) that carry micro RNAs and other factors to reprogram cancer cells and tissues affected by cancer. Exosomes are exchanged between cancer cells and other tissues, often to prepare a premetastatic niche, escape immune surveillance, or spread multidrug resistance. Only a few studies investigated the function of lipids in exosomes, although their lipid composition is different from that of the secreting cells. Ceramide is one of the lipids critical for exosome formation and it is also enriched in these EVs. New research suggests that lipids in the exosomal membrane may organize and transmit “mobile rafts” that turn exosomes into extracellular signalosomes spreading activation of cell signaling pathways in oncogenesis and metastasis. Ceramide may modulate the function of mobile rafts and their effect on these cell signaling pathways. The critical role of lipids and in particular, ceramide for formation, secretion, and function of exosomes may lead to a radically new understanding of cancer biology and therapy.

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Section: Exosomes In Cancer: Target Tissue Biohacking and Hijacking Omentioning

confidence: 99%

Ceramide and Exosomes: A Novel Target in Cancer Biology and Therapy

Elsherbini

Bieberich

2018

Advances in Cancer Research

114

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“…CD44 expression is upregulated under the postoperative inflammatory response, which involves elevated levels of reactive oxygen species, transforming growth factor-β1 (TGF-β1), interleukin-1β and tumor necrosis factor-α, leading to enhancement of cancer cell adhesion (32). Recently, Nakamura et al (33) co-cultured human peritoneal mesothelial cells (HPMCs) with exosomes derived from ovarian cancer cells and observed that HPMCs, which internalized TEX, exhibited higher level of CD44 expression and underwent mesothelial-to-mesenchymal transition (MMT). Additionally, CD44 overexpression in HPMCs promoted cancer invasion by inducing the HPMCs to secrete MMP9, in order to cross the mesothelial barrier.…”

Section: Exosomes In Peritoneal Dissemination Of Gastric Cancermentioning

confidence: 99%

“…Additionally, CD44 overexpression in HPMCs promoted cancer invasion by inducing the HPMCs to secrete MMP9, in order to cross the mesothelial barrier. By contrast, by knockdown of CD44 expression, TEX exerted fewer effects on HPMCs (33). Similarly, isolated exosomes from human gastric cancer cells have demonstrated expression of CD44H and CD44 variant exon 6 isoforms, which may serve a role in the attachment of TEX to cancer cells (34).…”

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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“…The pathogenesis of PF is characterized by a decreasing number of mesothelial cells and progressive submesothelial thickening with an increasing myofibroblast presence [23]. The accumulation of collagenproducing fibroblasts and excessive deposition of ECM disrupt normal peritoneal architecture and homeostasis [24].…”

Section: Molecular Network Of Fibrosis and Angiogenesis In Modulatingmentioning

confidence: 99%

Exosomes: The New Mediator of Peritoneal Membrane Function

Shi

Sheng³

2018

Kidney Blood Press Res

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Fibrosis and angiogenesis are the most common processes that result in progressive peritoneal tissue remodeling and, eventually, peritoneal membrane dysfunction. The role of exosomes, which contributes to intercellular communication, in these processes has been neglected. Various biomolecules, including DNA, mRNA, proteins, lipids, and particular certain miRNAs, can be transferred by exosomes to local, neighboring and distal cells. Upon stimulation by cytokines or other microenvironment stimuli, donor cells release a mass of exosomes to peritoneal mesothelial cells, further affecting fibrosis and angiogenesis. This important exosomes-mediated intracellular communication is thought to regulate peritoneal membrane function. Understanding the molecular mechanisms of these processes, targeting changes in exosomes and regulating exosomal miRNAs will advance therapeutic methods for protecting peritoneal membrane function.

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Exosomes Promote Ovarian Cancer Cell Invasion through Transfer of CD44 to Peritoneal Mesothelial Cells

Abstract: Mechanistic insight from the current study suggests that therapeutic targeting of exosomes may be beneficial in treating ovarian cancer. Mol Cancer Res; 15(1); 78-92. ©2016 AACR.

Cited by 187 publications

References 46 publications

Ceramide and Exosomes: A Novel Target in Cancer Biology and Therapy

Ceramide and Exosomes: A Novel Target in Cancer Biology and Therapy

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

Exosomes: The New Mediator of Peritoneal Membrane Function

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