Targeting β2-Adrenergic Receptors Shows Therapeutical Benefits in Clear Cell Renal Cell Carcinoma from Von Hippel–Lindau Disease

Albiñana, Virginia; Gallardo-Vara, Eunate; Rojas-P, Isabel de; Recio-Poveda, Lucía; Aguado, Tania; Canto-Cano, Ana; Aguirre, Daniel T; Serra, Marcelo; González‐Peramato, Pilar; Martínez‐Piñeiro, Luis; Cuesta, Ángel M.; Botella, Luisa María

doi:10.3390/jcm9092740

Cited by 13 publications

(23 citation statements)

References 59 publications

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“…Zahalka et al showed that the loss of endothelial ADRB2 weaken angiogenesis in prostate cancer (20). However, other reports also indicated that β2-AR activation significantly suppressed tumor growth (15,(21)(22)(23)(24). Sakakitani et al (24) demonstrated that β2-AR agonist inhibited cell motility and induced mesenchymal-epithelial transition in oral cancer.…”

Section: Introductionmentioning

confidence: 99%

ADRB2 is a potential protective gene in breast cancer by regulating tumor immune microenvironment

Wei¹,

Chen²,

Yang³

et al. 2021

Transl Cancer Res TCR

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Background: Breast cancer (BRCA) is the leading cause of cancer death among females. Studies suggested that β-adrenoceptors involved in tumor progression by regulating immune system. However, how ADRB2 affects the immune infiltration in BRCA is still being unraveled.Methods: Expressions of ADRB2 in multiple tissues, cancers and blood cells were analyzed by using the Human Protein Atlas and UALCAN database. Expression differentiation of ADRB2 in tumor microenvironment (TME) of BRCA was detected in TISCH database. Correlations between ADRB2 and immune cell infiltration were analyzed by TIMER 2.0, and co-expression genes of ADRB2 were obtained from the cBioPortal website. Functional enrichment analyses and protein-protein interactions were constructed as well. Finally, the potential mechanisms of ADRB2 and candidate drugs targeting BRCA were discussed by using the Metascape, STITCH and Cmap tools.Results: ADRB2 was significantly down-regulated in BRCA, and lower ADRB2 expression often resulted in worse prognosis in BRCA patients. ADRB2 was mainly expressed in breast tissue and blood. Among blood cell subtypes and TME of BRCA, ADRB2 was specifically expressed in T cell subtypes. Also, ADRB2 expression level was positively correlated with the infiltration levels of immune cells such as CD4+ T cell, CD8+ T cell, Tγδ and myeloid DC while negatively correlated with Treg, Tfh and myeloid-derived suppressor cell. Furthermore, functional enrichment analyses revealed that most enriched pathways were immune-related, especially in T cell-related pathways. Also, transcription factors (TFs) analyses showed that most downstream TFs regulated by ADRB2 were immune-related, and most candidate drugs had promising anti-tumor effects.Conclusions: In conclusion, ADRB2 was a potential protective gene in BRCA, and it might play a vital role in regulating immune responses. The expression level of ADRB2 was positively correlated with immune cells infiltration in BRCA, especially for T cells. Therefore, ADRB2 would be a target for boosting immunotherapy effects in BRCA.

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Section: Introductionmentioning

confidence: 99%

ADRB2 is a potential protective gene in breast cancer by regulating tumor immune microenvironment

Wei¹,

Chen²,

Yang³

et al. 2021

Transl Cancer Res TCR

View full text Add to dashboard Cite

show abstract

“…The current systemic therapeutic approaches include: targeting pathways of angiogenesis, immune checkpoint blockade, and mTOR inhibition. By inducing smooth muscle relaxation and vasodilation, these drugs are used for the treatment of hypertension (HTN) and obstructive symptoms associated with BPH (as discussed above) [216,217]. This mechanism of action is also utilized in the treatment of renal and ureteric stones, as α1 blockers reduce intraureteral pressure and increase fluid passage [216].…”

Section: Renal Cancermentioning

confidence: 99%

“…Doxazosin and naftodipil, selective α1-adrenoceptor antagonists, inhibit the proliferation of RCC cells both in vitro and in vivo human tumor xenografts in mice [47,213]. Propranolol induces loss of cell viability in RCC cells in vitro by increasing gene expression involved in apoptosis, decreasing HIF-α expression, and inhibiting the NFκB survival signaling [216,217]. α-1 blockade has been linked to an increased RCC incidence, although the study is limited by confounding factors such as concurrent BPH or HTN [224].…”

Section: Renal Cancermentioning

confidence: 99%

Role of α- and β-adrenergic signaling in phenotypic targeting: significance in benign and malignant urologic disease

et al. 2021

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The urinary tract is highly innervated by autonomic nerves which are essential in urinary tract development, the production of growth factors, and the control of homeostasis. These neural signals may become dysregulated in several genitourinary (GU) disease states, both benign and malignant. Accordingly, the autonomic nervous system is a therapeutic target for several genitourinary pathologies including cancer, voiding dysfunction, and obstructing nephrolithiasis. Adrenergic receptors (adrenoceptors) are G-Protein coupled-receptors that are distributed throughout the body. The major function of α1-adrenoceptors is signaling smooth muscle contractions through GPCR and intracellular calcium influx. Pharmacologic intervention of α-and β-adrenoceptors is routinely and successfully implemented in the treatment of benign urologic illnesses, through the use of α-adrenoceptor antagonists. Furthermore, cell-based evidence recently established the antitumor effect of α1-adrenoceptor antagonists in prostate, bladder and renal tumors by reducing neovascularity and impairing growth within the tumor microenvironment via regulation of the phenotypic epithelial-mesenchymal transition (EMT). There has been a significant focus on repurposing the routinely used, Food and Drug Administration-approved α1-adrenoceptor antagonists to inhibit GU tumor growth and angiogenesis in patients with advanced prostate, bladder, and renal cancer. In this review we discuss the current evidence on (a) the signaling events of the autonomic nervous system mediated by its cognate α- and β-adrenoceptors in regulating the phenotypic landscape (EMT) of genitourinary organs; and (b) the therapeutic significance of targeting this signaling pathway in benign and malignant urologic disease.

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“…In addition, novel drugs have been developed based on the key pathways involved in HGB development, and their safety and effectiveness are being evaluated by several clinical studies (1,6,40,41). These medications include antiangiogenic agents, anti-VEGF agents, histone deacetylase inhibitors and inhibitors designed for HIFs (6,42,43). Among them, antiangiogenic agents were reported to halt tumor growth in RCC, and anti-VEGF agents may be more suitable for retinal HGBs and CNS HGBs (44)(45)(46).…”

Section: Treatmentmentioning

confidence: 99%

Central Nervous System Hemangioblastoma in a Pediatric Patient Associated With Von Hippel-Lindau Disease: A Case Report and Literature Review

Yang

Wang

et al. 2021

Front. Oncol.

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BackgroundHemangioblastoma is a benign tumor of the central nervous system and may appear as a component of von Hippel-Lindau (VHL) disease. At present, approximately 40 cases of optic nerve HGBs have been reported in the literature. VHL disease is a rare autosomal-dominant inherited cancer syndrome with different phenotypes caused by variants in the VHL gene. Herein, the authors describe a case of a pediatric patient with VHL disease and with optic nerve HGB, a rare phenotypic expression. The purpose of this study was to explore the genotype-phenotype, clinical features, treatment and follow-up of VHL-associated hemangioblastomas in pediatric patients.Case DescriptionA 12-year-old boy presented with vision loss, headache and dizziness at our hospital. Magnetic resonance imaging (MRI) revealed a large (19.8 mm*18.5 mm*23.5 mm) irregular mass located in the suprasellar region. The mass was successfully removed after craniotomy and microsurgical treatment. The pathological diagnosis was left optic nerve HGB. Genetic analyses showed p.Pro86Leu (c. 257C>T) heterozygous missense mutations in the VHL gene.ConclusionThis is the first reported pediatric case of VHL-associated optic nerve HGB. The genotype-phenotype correlation of VHL disease may provide new evidences for predicting tumor penetrance and survival. Gross tumor resection combined with stereotactic radiosurgery might be the most beneficial treatment.

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Targeting β2-Adrenergic Receptors Shows Therapeutical Benefits in Clear Cell Renal Cell Carcinoma from Von Hippel–Lindau Disease

Cited by 13 publications

References 59 publications

ADRB2 is a potential protective gene in breast cancer by regulating tumor immune microenvironment

ADRB2 is a potential protective gene in breast cancer by regulating tumor immune microenvironment

Role of α- and β-adrenergic signaling in phenotypic targeting: significance in benign and malignant urologic disease

Central Nervous System Hemangioblastoma in a Pediatric Patient Associated With Von Hippel-Lindau Disease: A Case Report and Literature Review

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