Exosome-mediated transfer of CD44 from high-metastatic ovarian cancer cells promotes migration and invasion of low-metastatic ovarian cancer cells

Shen, Xiameng; Wang, Conghui; Zhu, Huihui; Wang, Yaping; Wang, Xinyu; Cheng, Xiaodong; Ge, Wanzhong; Lü, Weiguo

doi:10.1186/s13048-021-00776-2

Cited by 39 publications

(36 citation statements)

References 52 publications

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“…These data support the hypothesis that ovarian cancer cells utilize extracellular vesicle signaling between cancer cells to propagate chemoresistance. Furthermore, the data obtained are consistent with recent studies that implicate extracellular vesicles in hypoxia-induced metabolic changes within the pre-metastatic milieu [38][39][40] and in the acquisition of chemoresistance [41][42][43][44][45][46].…”

Section: Discussionsupporting

confidence: 90%

Extracellular Vesicle Transmission of Chemoresistance to Ovarian Cancer Cells Is Associated with Hypoxia-Induced Expression of Glycolytic Pathway Proteins, and Prediction of Epithelial Ovarian Cancer Disease Recurrence

Alharbi

Lai

Sharma

et al. 2021

Cancers

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Hypoxia is a key regulator of cancer progression and chemoresistance. Ambiguity remains about how cancer cells adapt to hypoxic microenvironments and transfer oncogenic factors to surrounding cells. In this study, we determined the effects of hypoxia on the bioactivity of sEVs in a panel of ovarian cancer (OvCar) cell lines. The data obtained demonstrate a varying degree of platinum resistance induced in OvCar cells when exposed to low oxygen tension (1% oxygen). Using quantitative mass spectrometry (Sequential Window Acquisition of All Theoretical Fragment Ion Mass Spectra, SWATH) and targeted multiple reaction monitoring (MRM), we identified a suite of proteins associated with glycolysis that change under hypoxic conditions in cells and sEVs. Interestingly, we identified a differential response to hypoxia in the OvCar cell lines and their secreted sEVs, highlighting the cells’ heterogeneity. Proteins are involved in metabolic reprogramming such as glycolysis, including putative hexokinase (HK), UDP-glucuronosyltransferase 1–6 (UD16), and 6-phosphogluconolactonase (6 PGL), and their presence correlates with the induction of platinum resistance. Furthermore, when normoxic cells were exposed to sEVs from hypoxic cells, platinum-resistance increased significantly (p < 0.05). Altered chemoresistance was associated with changes in glycolysis and fatty acid synthesis. Finally, sEVs isolated from a clinical cohort (n = 31) were also found to be enriched in glycolysis-pathway proteins, especially in patients with recurrent disease. These data support the hypothesis that hypoxia induces changes in sEVs composition and bioactivity that confers carboplatin resistance on target cells. Furthermore, we propose that the expression of sEV-associated glycolysis-pathway proteins is predictive of ovarian cancer recurrence and is of clinical utility in disease management.

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Section: Discussionsupporting

confidence: 90%

Extracellular Vesicle Transmission of Chemoresistance to Ovarian Cancer Cells Is Associated with Hypoxia-Induced Expression of Glycolytic Pathway Proteins, and Prediction of Epithelial Ovarian Cancer Disease Recurrence

Alharbi

Lai

Sharma

et al. 2021

Cancers

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“…Studies have demonstrated that exosome-mediated transfer of key proteins plays an essential role in ovarian carcinogenesis. 90 , 91 For instance, the migration and invasion of low-metastatic ovarian cancer cells were enhanced due to exosome-involved transfer of CD44 from high-metastatic ovarian cancer cells. 90 Exosomes derived from ovarian cancer cells transported CD44 to human peritoneal mesothelial cells, thus increasing the invasive ability of ovarian cancer.…”

Section: The Role Of Exosome-carried Proteins In Ovarian Cancermentioning

confidence: 99%

Nucleic acids and proteins carried by exosomes of different origins as potential biomarkers for gynecologic cancers

Wang

Pan

Zheng

et al. 2022

Molecular Therapy - Oncolytics

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Exosomes are extracellular vesicles with a diameter of 30–150 nm that function in mediating intercellular communication and intercellular material exchange. The liposomal membrane of exosomes protects the cargo carried by exosomes from degradation and assists in transporting cargo to recipient cells to regulate a variety of physiological and pathological processes. The incidence of gynecologic cancers is increasing annually, which is extremely harmful to the lives and health of women because such cancers are challenging to detect at the early stage. Recently, exosomes have emerged as novel biomarkers for diagnosing and predicting the development of gynecologic cancers. In particular, non-coding RNAs (microRNAs [miRNAs], long non-coding RNAs [lncRNAs], and circular RNAs [circRNAs]) carried by exosomes have been extensively investigated in gynecologic cancers. Therefore, the purpose of this review is to focus on the potential roles of exosomes of different origins in ovarian cancer, cervical cancer, and endometrial cancer, which will help to determine the molecular mechanism of carcinogenesis.

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“…Fourth, exosomes lack toxicity and immunogenicity (228). It has been evident from various studies (229)(230)(231)(232) that exosomes and their contents have the innate ability to govern cell survival, proliferation, migration, and differentiation in the damaged heart; thereby, reducing the risk of CVD-related deaths.…”

Section: Advantages Of Exosomesmentioning

confidence: 99%

Stem Cell-Derived Exosomes Potential Therapeutic Roles in Cardiovascular Diseases

Jayaraman

Gnanasampanthapandian

Rajasingh

et al. 2021

Front. Cardiovasc. Med.

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Owing to myocardial abnormalities, cardiac ailments are considered to be the major cause of morbidity and mortality worldwide. According to a recent study, membranous vesicles that are produced naturally, termed as “exosomes”, have emerged as the potential candidate in the field of cardiac regenerative medicine. A wide spectrum of stem cells has also been investigated in the treatment of cardiovascular diseases (CVD). Exosomes obtained from the stem cells are found to be cardioprotective and offer great hope in the treatment of CVD. The basic nature of exosomes is to deal with the intracellular delivery of both proteins and nucleic acids. This activity of exosomes helps us to rely on them as the attractive pharmaceutical delivery agents. Most importantly, exosomes derived from microRNAs (miRNAs) hold great promise in assessing the risk of CVD, as they serve as notable biomarkers of the disease. Exosomes are small, less immunogenic, and lack toxicity. These nanovesicles harbor immense potential as a therapeutic entity and would provide fruitful benefits if consequential research were focused on their upbringing and development as a useful diagnostic and therapeutic tool in the field of medicine.

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Exosome-mediated transfer of CD44 from high-metastatic ovarian cancer cells promotes migration and invasion of low-metastatic ovarian cancer cells

Cited by 39 publications

References 52 publications

Extracellular Vesicle Transmission of Chemoresistance to Ovarian Cancer Cells Is Associated with Hypoxia-Induced Expression of Glycolytic Pathway Proteins, and Prediction of Epithelial Ovarian Cancer Disease Recurrence

Extracellular Vesicle Transmission of Chemoresistance to Ovarian Cancer Cells Is Associated with Hypoxia-Induced Expression of Glycolytic Pathway Proteins, and Prediction of Epithelial Ovarian Cancer Disease Recurrence

Nucleic acids and proteins carried by exosomes of different origins as potential biomarkers for gynecologic cancers

Stem Cell-Derived Exosomes Potential Therapeutic Roles in Cardiovascular Diseases

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