Pituitary Somatotroph Adenoma-derived Exosomes: Characterization of Nonhormonal Actions

Zhou, Cuiqi; Shen, Stephen; Moran, Rosemary; Deng, Nan; Marbán, Eduardo; Melmed, Shlomo

doi:10.1210/clinem/dgab651

Cited by 12 publications

(6 citation statements)

References 55 publications

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“…In our study, we assessed the alterations in serum miRNA levels during radiotherapy. It has been reported that the levels of miRNAs in cells and those derived from serum exosomes are essentially concordant [ 45 ]. The upregulation of serum miR-143-3p and miR-223-3p levels during radiotherapy could serve as an early indicator of radiosensitivity in ESCC, displaying an AUC ≥ 0.7 in predicting both OS and PFS.…”

Section: Discussionmentioning

confidence: 99%

Tumor-Derived Exosomal miR-143-3p Induces Macrophage M2 Polarization to Cause Radiation Resistance in Locally Advanced Esophageal Squamous Cell Carcinoma

Gao,

Zhang,

Huang

et al. 2024

IJMS

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We aimed to determine whether monitoring tumor-derived exosomal microRNAs (miRNAs) could be used to assess radiotherapeutic sensitivity in patients with locally advanced esophageal squamous cell carcinoma (ESCC). RNA sequencing was employed to conduct a comparative analysis of miRNA expression levels during radiotherapy, focusing on identifying miRNAs associated with progression. Electron microscopy confirmed the existence of exosomes, and co-cultivation assays and immunofluorescence validated their capacity to infiltrate macrophages. To determine the mechanism by which exosomal miR-143-3p regulates the interplay between ESCC cells and M2 macrophages, ESCC cell-derived exosomes were co-cultured with macrophages. Serum miR-143-3p and miR-223-3p were elevated during radiotherapy, suggesting resistance to radiation and an unfavorable prognosis for ESCC. Increased levels of both miRNAs independently predicted shorter progression-free survival (p = 0.015). We developed a diagnostic model for ESCC using serum microRNAs, resulting in an area under the curve of 0.751. Radiotherapy enhanced the release of miR-143-3p from ESCC cell-derived exosomes. Immune cell infiltration analysis at the Cancer Genome Atlas (TCGA) database revealed that ESCC cell-derived miR-143-3p triggered M2 macrophage polarization. Mechanistically, miR-143-3p upregulation affected chemokine activity and cytokine signaling pathways. Furthermore, ESCC cell exosomal miR-143-3p could be transferred to macrophages, thereby promoting their polarization. Serum miR-143-3p and miR-223-3p could represent diagnostic and prognostic markers for patients with ESCC undergoing radiotherapy. Unfavorable prognosis could be linked to the increased levels of ESCC cell-derived exosomal miR-143-3p, which might promote tumor progression by interacting with macrophages.

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Section: Discussionmentioning

confidence: 99%

Tumor-Derived Exosomal miR-143-3p Induces Macrophage M2 Polarization to Cause Radiation Resistance in Locally Advanced Esophageal Squamous Cell Carcinoma

Gao,

Zhang,

Huang

et al. 2024

IJMS

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“…It is worth mentioning that there are only a few studies about the role of EVs in the hypothalamus and most of them concern POMC neurons [213][214][215]. There are, however, several studies regarding pituitary EVs, mainly in an attempt to determine biomarkers of pituitary adenomas [416][417][418]. In a recent study, hydrocortisone stimulated the release of EVs from pituitary somatotroph cells [417].…”

Section: Discussionmentioning

confidence: 99%

“…There are, however, several studies regarding pituitary EVs, mainly in an attempt to determine biomarkers of pituitary adenomas [416][417][418]. In a recent study, hydrocortisone stimulated the release of EVs from pituitary somatotroph cells [417].…”

Section: Discussionmentioning

confidence: 99%

Extracellular Vesicles and the Stress System

Makrygianni

Chrousos

2022

Neuroendocrinology

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Extracellular vesicles (EVs) are membrane-enclosed nanoparticles that contain various biomolecules, including nucleic acids, proteins, and lipids, and are manufactured and released by virtually all cell types. There is evidence that EVs are involved in intercellular communication, acting in an autocrine, paracrine, or/and endocrine manner. EVs are released by the cells of the central nervous system (CNS), including neurons, astrocytes, oligodendrocytes and microglia, and have the ability to cross the blood brain barrier (BBB) and enter the systemic circulation. Neuroendocrine cells are specialized neurons that secrete hormones directly into blood vessels, such as the hypophyseal portal system or the systemic circulation, a process that allows neuroendocrine integration to take place. In mammals, neuroendocrine cells are widely distributed throughout various anatomic compartments, with the hypothalamus being a central neuroendocrine integrator. The hypothalamus is a key part of the Stress System (SS), a highly conserved neuronal/neuroendocrine system aiming at maintaining systemic homeostasis, when the latter is threatened by various stressors. The central parts of the SS are the interconnected hypothalamic Corticotropin-releasing Hormone (CRH) and the brainstem Locus Caeruleus-Norepinephrine (LC-NE) systems, while their peripheral parts are respectively the pituitary-adrenal axis, and the sympathetic nervous/sympatho-adrenomedullary systems (SNS-SAM) as well as components of the parasympathetic system (PNS). During stress, multiple CNS loci show plasticity and undergo remodeling, partly mediated by increased glutamatergic and noradrenergic activity, and actions of cytokines and glucocorticoids (GCs), all regulated by the interaction of the hypothalamic-pituitary-adrenal (HPA) axis and the LC-NE/SNS-SAM systems. In addition, there are peripheral changes due to the increased secretion of stress hormones and pro-inflammatory cytokines in the context of stress-related systemic (para)inflammation.

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“…Interestingly, Zhou et al reported that exosomes of GHPA cell line treated colon cancer cell line (HCT116 cell line) showed decreased malignancy in vitro and decreased tumor metastasis in HCT116 xenografted nude mice (11). This decreased malignancy occurs proposed through altered gene expression in the p53 and MAPK pathways (11). In addition, Zhao et al indicates that low miR-423-5p levels promote tumorigenesis in somatotropic adenomas (53).…”

Section: Ghpasmentioning

confidence: 99%

“…The secretory quantity and content of exosomes can vary according to their biogenesis, cell of origin, and physiological or pathological cell status. Among these, noncoding RNAs (ncRNAs) are enriched and stable in exosomes and are important owing to their regulatory function in tumor initiation and progression, including in PA (10,11).…”

Section: Introductionmentioning

confidence: 99%

Exosomal RNAs in the development and treatment of pituitary adenomas

Chang

Jiang²,

Guo³

et al. 2023

Front. Endocrinol.

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Exosomes are small extracellular vesicles that carry various bioactive molecules including various RNAs that modulate the activities of recipient cells. It has drawn considerable attention as means of cell communication and drug delivery. Exosome plays important role in various tumors, but it is rarely summarized in pituitary adenoma (PA). PA is the second most common primary central nervous system tumor, and its recurrence and persistent postoperative hormone hypersecretion lead to compromised quality of life. How exactly exosomes impact tumor development and hormone secretion is important for the development of this tumor diagnosis and treatment. In this review, we discuss how exosomal RNAs impact PAs and their potential as future clinical therapies. In our literature review, first, we found that exosomal microRNA hsa-miR-1180-3p is a potential early biomarker for NFPAs. Since NFPAs are typically difficult to diagnose, this is an especially important finding. Second, exosomal protein transcripts are potential invasive biomarker, such as MMP1, N-cadherin, CDK6, RHOU, INSM1, and RASSF10. Third, exosomal contents such as hsa-miR-21-5p promote distant bone formation of GHPA patients. Fourth, tumor suppressors in the exosome constitute novel therapeutic application of exosome, including long noncoding RNA (lncRNA) H19, miR-149-5p, miR-99a-3p, and miR-423-5p. This review discusses the possible mechanisms of exosome and their contents in PA and promotes the use of exosomes in both clinical diagnosis and treatment of this tumor.

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Pituitary Somatotroph Adenoma-derived Exosomes: Characterization of Nonhormonal Actions

Cited by 12 publications

References 55 publications

Tumor-Derived Exosomal miR-143-3p Induces Macrophage M2 Polarization to Cause Radiation Resistance in Locally Advanced Esophageal Squamous Cell Carcinoma

Tumor-Derived Exosomal miR-143-3p Induces Macrophage M2 Polarization to Cause Radiation Resistance in Locally Advanced Esophageal Squamous Cell Carcinoma

Extracellular Vesicles and the Stress System

Exosomal RNAs in the development and treatment of pituitary adenomas

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