Exosomes from the tumor microenvironment as reciprocal regulators that enhance prostate cancer progression

Liu, Che Ming; Hsieh, Chia Ling; Shen, Chia‐Ning; Lin, Cheng Chieh; Shigemura, Katsumi; Sung, Shian Ying

doi:10.1111/iju.13145

Cited by 39 publications

(41 citation statements)

References 139 publications

(131 reference statements)

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“…The study of organ‐specific metastasis to the brain has been gradually gaining recognition nowadays. Nevertheless, a lot of brain‐derived factors are developed in recent studies, including secreted proteins and microRNA‐containing exosomes which alter the brain microenvironment to facilitate the survival and growth of BM 12, 13. Extracellular vesicles (EVs) including exosomes, mediate cell to cell communication with the delivery of their contents and then adjust multiple factors of malignancy in cancer cells 14, 15.…”

Section: The Hypothesis About the Origin Of Bmmentioning

confidence: 99%

Emerging findings into molecular mechanism of brain metastasis

Chen

2018

Cancer Medicine

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Brain metastasis is an important cause of morbidity and mortality in cancer patients. Hence, the need to develop improved therapies to prevent and treat metastasis to the brain is becoming urgent. Recent studies in this area are bringing about some advanced progress on brain metastasis. It was concluded that the occurrence and poor prognosis of brain metastasis have been mostly attributed to the exclusion of anticancer drugs from the brain by the blood‐brain barrier. And several highly potent new generation targeted drugs with enhanced CNS distribution have been developed constantly. However, the noted “seed and soil” hypothesis also suggests that the outcome of metastasis depends on the relationship between unique tumor cells and the specific organ microenvironment. Moreover, increasing studies in multiple tumor types demonstrated that brain metastasis has great molecular differences between primary tumors and extracranial metastasis to a large extent. Here, the authors summarized the most common malignancies that could lead to brain metastasis—lung cancer, breast cancer and melanoma and their related mutated factors. Only by comprehending a deeper understanding of the molecular mechanisms, more effective brain‐specific therapies will be developed for brain metastasis.

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Section: The Hypothesis About the Origin Of Bmmentioning

confidence: 99%

Emerging findings into molecular mechanism of brain metastasis

Chen

2018

Cancer Medicine

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“…The canonical proteins in exosomes could be identi ed, such as heat shock proteins, cytoskeletal proteins, endosomal molecules, multivesicular tetraspanins, antigen presentation molecules, adhesion proteins, immunoglobulin family members, and so on [21]. Moreover, exosomal proteins speci c for DU145 cells were detected, exempli ed by integrin family members, CD276, ANXA2, CLSTN1, FASN, and FLNC [7]. These results demonstrated that exosomes from PC DU145 cells not only have similar features as exosomes from other cell types but also have speci c characteristics.…”

Section: Discussionmentioning

confidence: 99%

“…It has been proved that tumor-derived exosomes can be uptaken by speci c organs or cells, to create favorable TME for cancer metastasis. For example, miR-21, miR-141, and miR-375 enriched exosomes derived from PC play important roles in assisting tumor cells to acclimatize to the low-androgen environment of distant metastatic organs [7].…”

Section: Introductionmentioning

confidence: 99%

Proteomic Profiling of Du145 Cell Line Exosomes Identifies Icam1 as Aputative molecular Mechanism by Which Relb Promotes The proliferation, Migration, and Invasion of Prostate cancer Cells

Li¹,

Xu²,

Li³

et al. 2020

Preprint

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Background: Prostate cancer (PC) is a serious health issue in men. Exosome plays essential roles in modulating the oncogenesis and progression of PC. RelB is highly expressed in PC and plays oncogenic parts in DU145 cells. We aim to uncover the protein panel of exosomes derived from RelB-knockdown DU145 cells (siRelB) as compared to control cells (sictrl) and explore a potential mechanism that RelB conferring the more aggressive phenotype to DU145 cells.Methods: Exosomes derived from sictrl and siRelB were subjected to Liquid Chromatography-Mass Spectrometry for proteomics profiling. Label-free quantification strategy iBAQ (intensity-based absolute quantification) was used to quantify and Fold Change (FC) was calculated to identify the differentially expressed proteins (DEPs). The characterization of proteins was conducted by bioinformatics analysis. ICAM1 over-expressing DU145 cells (hICAM1) and control cells (hctrl) were established by transfection using Lipofectamine 2000. The cell growth, migration, and invasion capabilities were measured by the xCelligence real-time monitoring system. Annexin V/PI-staining was adopted to assess apoptosis. CCK-8 assay was applied for proliferation evaluation. Integrin β-1, MMP9, and uPA were detected by Western blot.Results: 1259 exosomal proteins were identified, with 160 and 105 proteins unique to the siRelB and sictrl, respectively, while 994 proteins were present in both. We identified 137 upregulated and 55 downregulated proteins in siRelB. Gene Ontology (GO) analysis revealed that some DEPs had the cell adhesion molecular activity and participated in the cell adhesion process. Kyoto Encyclopedia of Genes and Genomes (KEGG) enriched that intercellular adhesion molecule-1 (ICAM1) was downregulated targeted by the NF-κB signaling. The FC of exosomal ICAM1 was 2.136. The expression of ICAM1 was positively related to RelB in PC by UALCAN. ICAM1 was shown to be co-expressed with RelB by GeneMANIA. The protein abundance of exosomal ICAM1 was lower in siRelB. hICAM1 had enhanced abilities of proliferation, migration, and invasion, with higher expression of Integrin β-1 when compared to hctrl.Conclusions: Our study identified 192 exosomal DEPs downstream of RelB in the DU145 cells. Exosomal ICAM1, conferring a more aggressive phenotype to DU145 cells, is a potential molecular mechanism modulating the tumorigenesis and progression of PC cells.

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“…Recent studies point out that exosomes released from the tumor microenvironment can regulate (also by tethering TGFβ) a proliferation, a reduction of apoptosis, a promotion of angiogenesis and, finally, an evasion of immune surveillance ( Figure 2). Moreover, exosomes can provide candidate biomarkers for prostate cancer, contribute to tumor progression and, after a loss of environment homeostasis, promote tumor metastasis [18]. Role of prostate cell-derived exosomes in cancer progression.…”

Section: Introductionmentioning

confidence: 99%

Exosomes in Prostate Cancer Diagnosis, Prognosis and Therapy

Lorenc

Klimczyk

Michalczewska

et al. 2020

IJMS

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Prostate cancer (PCa) is the second most common cause of cancer-related mortality among men in the developed world. Conventional anti-PCa therapies are not effective for patients with advanced and/or metastatic disease. In most cases, cancer therapies fail due to an incomplete depletion of tumor cells, resulting in tumor relapse. Exosomes are involved in tumor progression, promoting the angiogenesis and migration of tumor cells during metastasis. These structures contribute to the dissemination of pathogenic agents through interaction with recipient cells. Exosomes may deliver molecules that are able to induce the transdifferentiation process, known as "epithelial to mesenchymal transition". The composition of exosomes and the associated possibilities of interacting with cells make exosomes multifaceted regulators of cancer development. Extracellular vesicles have biophysical properties, such as stability, biocompatibility, permeability, low toxicity and low immunogenicity, which are key for the successful development of an innovative drug delivery system. They have an enhanced circulation stability and bio-barrier permeation ability, and they can therefore be used as effective chemotherapeutic carriers to improve the regulation of target tissues and organs. Exosomes have the capacity to deliver different types of cargo and to target specific cells. Chemotherapeutics, natural products and RNA have been encapsulated for the treatment of prostate cancers.

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Exosomes from the tumor microenvironment as reciprocal regulators that enhance prostate cancer progression

Cited by 39 publications

References 139 publications

Emerging findings into molecular mechanism of brain metastasis

Emerging findings into molecular mechanism of brain metastasis

Proteomic Profiling of Du145 Cell Line Exosomes Identifies Icam1 as Aputative molecular Mechanism by Which Relb Promotes The proliferation, Migration, and Invasion of Prostate cancer Cells

Exosomes in Prostate Cancer Diagnosis, Prognosis and Therapy

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