Exosomes expressing carbonic anhydrase 9 promote angiogenesis

Horie, Kengo; Kawakami, Kyojiro; Fujita, Yasunori; Sugaya, Maki; Kameyama, Koji; Mizutani, Kosuke; Deguchi, Takashi; Ito, Masafumi

doi:10.1016/j.bbrc.2017.08.107

Cited by 95 publications

(80 citation statements)

References 23 publications

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“…Western blot analysis, as well as ELISA, enabled us to reveal mCA IX protein expression in exosomes isolated from both cell lines. In addition, consistent with the intracellular expression level, the expression of mCA IX was evidently higher in exosomes isolated from B16-F0 and L-929 cells grown in hypoxia for 48 h. Similarly, Horie and colleagues found that CA IX was elevated in exosomes isolated from several renal carcinoma cell lines following hypoxia or treatment with CoCl 2 (a hypoxia mimic agent) [25]. Interestingly, we observed that hypoxia also affected the production of exosomes, and thus, the concentration of exosomes isolated from hypoxic murine cells was higher than in the normoxic counterparts.…”

Section: Discussionsupporting

confidence: 55%

“…Since human CA IX has been detected in exosomes isolated from renal and prostate cancer cell lines [25,26], we hypothesized that exosomes expressing mCA IX could be released from murine B16-F0 and L-929 cell lines. Western blot analysis, as well as ELISA, enabled us to reveal mCA IX protein expression in exosomes isolated from both cell lines.…”

Section: Discussionmentioning

confidence: 99%

“…CA IX as a transmembrane protein can also be detected as a soluble metalloprotease-cleaved form or as a soluble membrane-bound form released on cell-derived exosomes [23][24][25][26]. We were, therefore, interested in identifying and characterizing extracellular forms of mCA IX, because of all the above-mentioned functional similarities identified between both orthologs.…”

Section: Extracellular Forms Of Mca Ix-mca IX Ectodomain Sheddingmentioning

confidence: 99%

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Carbonic Anhydrase IX—Mouse versus Human

Takáčová

Baráthová

Zaťovičová

et al. 2019

IJMS

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In contrast to human carbonic anhydrase IX (hCA IX) that has been extensively studied with respect to its molecular and functional properties as well as regulation and expression, the mouse ortholog has been investigated primarily in relation to tissue distribution and characterization of CA IX-deficient mice. Thus, no data describing transcriptional regulation and functional properties of the mouse CA IX (mCA IX) have been published so far, despite its evident potential as a biomarker/target in pre-clinical animal models of tumor hypoxia. Here, we investigated for the first time, the transcriptional regulation of the Car9 gene with a detailed description of its promoter. Moreover, we performed a functional analysis of the mCA IX protein focused on pH regulation, cell-cell adhesion, and migration. Finally, we revealed an absence of a soluble extracellular form of mCA IX and provided the first experimental evidence of mCA IX presence in exosomes. In conclusion, though the protein characteristics of hCA IX and mCA IX are highly similar, and the transcription of both genes is predominantly governed by hypoxia, some attributes of transcriptional regulation are specific for either human or mouse and as such, could result in different tissue expression and data interpretation.

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Section: Discussionsupporting

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Section: Extracellular Forms Of Mca Ix-mca IX Ectodomain Sheddingmentioning

confidence: 99%

See 1 more Smart Citation

Carbonic Anhydrase IX—Mouse versus Human

Takáčová

Baráthová

Zaťovičová

et al. 2019

IJMS

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“…Hypoxia regulates the expression of many genes inducing a phenotypic alteration of stromal cells in the tumour microenvironment and promoting the survival of cancer cells. Low oxygen activates the HIF-1, the hypoxia-inducible factor 1 (HIF-1) 47,48 , which starts the transcription of several hypoxia-inducible genes, such as (Vascular Endothelial Growth Factor (VEGF), Glucose Transporter 1 (GLUT1), CA IX and CA XII)) 49 . CA IX is one of the most potent hypoxia-induced proteins, and the hypoxia-inducible proteins are important anti-cancer targets 50 .…”

Section: Tumour-associated Ca IXmentioning

confidence: 99%

“…These data strongly support that exosomes and CA IX are tumour-associated components and the enzyme CA IX is a cancer biomarker that could be used as valuable target of the liquid biopsy 82 . Horie et al demonstrated that CA IX exosomes were released from renal carcinoma cells 49 . The quantity of exosomal CA IX is increased in hypoxia response, promoting upregulation of MMP-2, migration and tube formation, and may induce angiogenesis in the tumour microenvironment 49 .…”

Section: Tumour-associated Ca IX As Biomarker In Liquid Biopsymentioning

confidence: 99%

Carbonic anhydrase IX as a novel candidate in liquid biopsy

Guler

Supuran

Capasso

2019

Journal of Enzyme Inhibition and Medicinal Chemistry

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Among the diagnostic techniques for the identification of tumour biomarkers, the liquid biopsy is considered one that offers future research on precision diagnosis and treatment of tumours in a non-invasive manner. The approach consists of isolating tumor-derived components, such as circulating tumour cells (CTC), tumour cell-free DNA (ctDNA), and extracellular vesicles (EVs), from the patient peripheral blood fluids. These elements constitute a source of genomic and proteomic information for cancer treatment. Within the tumour-derived components of the body fluids, the enzyme indicated with the acronym CA IX and belonging to the superfamily of carbonic anhydrases (CA, EC 4.2.1.1) is a promising aspirant for checking tumours. CA IX is a transmembrane-CA isoform that is strongly overexpressed in many cancers being not much diffused in healthy tissues except the gastrointestinal tract. Here, it is summarised the role of CA IX as tumour-associated protein and its putative relationship in liquid biopsyfor diagnosing and monitoring cancer progression. ARTICLE HISTORY

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Tumor‐derived exosomes: Implication in angiogenesis and antiangiogenesis cancer therapy

Aslan

Maralbashi

Salari

et al. 2019

Journal Cellular Physiology

110

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Tumor cells utilize different strategies to communicate with neighboring tissues for facilitating tumor progression and invasion, one of these strategies has been shown to be the release of exosomes. Exosomes are small nanovesicles secreted by all kind of cells in the body, especially cancer cells, and mediate cell to cell communications. Exosomes play an important role in cancer invasiveness by harboring various cargoes that could accelerate angiogenesis. Here first, we will present an overview of exosomes, their biology, and their function in the body. Then, we will focus on exosomes derived from tumor cells as tumor angiogenesis mediators with a particular emphasis on the underlying mechanisms in various cancer origins. Also, exosomes derived from stem cells and tumor‐associated macrophages will be discussed in this regard. Finally, we will discuss the novel therapeutic strategies of exosomes as drug delivery vehicles against angiogenesis.

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Exosomes expressing carbonic anhydrase 9 promote angiogenesis

Cited by 95 publications

References 23 publications

Carbonic Anhydrase IX—Mouse versus Human

Carbonic Anhydrase IX—Mouse versus Human

Carbonic anhydrase IX as a novel candidate in liquid biopsy

Tumor‐derived exosomes: Implication in angiogenesis and antiangiogenesis cancer therapy

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