Expression of transient receptor potential vanilloid‐1 (TRPV1) in urothelial cancers of human bladder: relation to clinicopathological and molecular parameters

Kalogris, Cristina; Caprodossi, Sara; Amantini, Consuelo; Lambertucci, Federica; Nabissi, Massimo; Morelli, Maria Beatrice; Farfariello, Valério; Filosa, Alessandra; Emiliozzi, Maria Cristina; Mammana, Gabriele; Santoni, Giorgio

doi:10.1111/j.1365-2559.2010.03683.x

Cited by 46 publications

(40 citation statements)

References 40 publications

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“…Within TRPM subfamily, the over-expression of TRPM7 was recently detected in UCB cells and it was regarded as a negative regulator of proliferation of UCB cell [25]. In contrast to the present study, in which TRPM8 expression is associated positively with UCB progression, an inverse correlation between TRPV1 expression and the tumor stage and grade in UCB tissues was demonstrated in another study [26]. However, skeptics deem that an altered expression of TRP channels may be simply an epiphenomenon to cancer progression and not a contributor to disease [27].…”

Section: Discussioncontrasting

confidence: 86%

Over-expression of TRPM8 is associated with poor prognosis in urothelial carcinoma of bladder

Xiao

Jiang

et al. 2014

Tumor Biol.

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Transient receptor protein (TRP) channels are frequently associated with tumors and are correlated to patient's outcome. We firstly investigated TRP channel melastatin 8 (TRPM8) expression in urothelial carcinoma of bladder (UCB) and its correlation with UCB clinicopathological features and additionally evaluated the association between TRPM8 expression and patients' survival rate to elucidate its role in bladder oncogenesis. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was conducted to examine TRPM8 messenger RNA (mRNA) expression in 36 pairs of freshly frozen UCB tissues and matched noncancerous tissues. Immunohistochemistry (IHC) was performed in 156 archived paraffin-embedded UCB samples to explore the correlation between TRPM8 protein and clinicopathological features. The association between TRPM8 expression and patient's survival rate was evaluated using the Kaplan-Meier method and multivariate Cox regression analysis, respectively. The expression levels of TRPM8 mRNA in UCB tissues were significantly higher than those in matched noncancerous tissues (P=0.016). Expression of TRPM8 protein in UCB was significantly and positively associated with histological grade (P=0.039) and tumor stage (P=0.037). Significant correlation between high TRPM8 expression and poor cumulative survival of UCB patients was shown using the Kaplan-Meier survival curve (P=0.039). TRPM8 was represented as an independent prognostic biomarker for UCB patients by multivariate Cox regression analysis (P=0.047). The present study provide the convincing evidence for the first time that over-expression of TRPM8 may play a role in the pathogenesis and progression of UCB, and TRPM8 may serve as an independent prognostic biomarker for UCB patients.

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Section: Discussioncontrasting

confidence: 86%

Over-expression of TRPM8 is associated with poor prognosis in urothelial carcinoma of bladder

Xiao

Jiang

et al. 2014

Tumor Biol.

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“…NGF is reported to increase TRPV1 mRNA expression, mediated in part by the transcription factor Sp1 (21), and may underlie our findings of parallels in expression of both genes in STZ-DM UT. Upregulation of TRPV1 in STZ-DM UT may serve as a cell "braking mechanism" on NGF-proliferative drive, preventing a transition in barrier repopulation/repair activity to one of tumorigenesis (42,51). In addition, whereas there was no indication of statistically significant changes in the inducible isoform of the cyclooxygenase gene COX2 in STZ-DM UT at all time points examined (Fig.…”

Section: J-l)mentioning

confidence: 71%

Impact of diabetes mellitus on bladder uroepithelial cells

Hanna-Mitchell

Ruiz

Daneshgari

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

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Diabetic bladder dysfunction (DBD), a prevalent complication of diabetes mellitus (DM), is characterized by a broad spectrum of symptoms including urinary urgency, frequency, and incontinence. As DBD is commonly diagnosed late, it is important to understand the chronic impact of DM on bladder tissues. While changes in bladder smooth muscle and innervation have been reported in diabetic patients, the impact of DM on the specialized epithelial lining of the urinary bladder, the urothelium (UT), is largely unknown. Quantitative polymerase chain reaction analysis and electron microscopy were used to evaluate UT gene expression and cell morphology 3, 9, and 20 wk following streptozotocin (STZ) induction of DM in female SpragueDawley rats compared with age-matched control tissue. Desquamation of superficial (umbrella) cells was noted at 9 wk DM, indicating a possible breach in barrier function. One causative factor may be metabolic burden due to chronic hyperglycemia, suggested by upregulation of the polyol pathway and glucose transport genes in DM UT. While superficial UT repopulation occurred by 20 wk DM, the phenotype was different, with significant upregulation of receptors associated with UT mechanosensation (transient receptor potential vanilloid subfamily member 1; TRPV1) and UT autocrine/paracrine signaling (acetylcholine receptors AChR-M2 and -M3, purinergic receptors P2X2 and P2X3). Compromised barrier function and alterations in UT mechanosensitivity and cell signaling could contribute to bladder instability, hyperactivity, and altered bladder sensation by modulating activity of afferent nerve endings, which appose the urothelium. Our results show that DM impacts urothelial homeostasis and may contribute to the underlying mechanisms of DBD. streptozotocin; urothelium; barrier; sensory; diabetic bladder dysfunction IN THE UNITED STATES alone it is estimated that approximately 19 million individuals, comprising both men and women, suffer from diabetes mellitus (DM) (13). DM is characterized by defects in the secretion of the hormone insulin by the pancreas and/or insulin signaling (53), which causes a dysregulation of cellular glucose uptake. Glucose is a large hydrophilic molecule that depends on specific glucose transporter (GLUT) proteins, present on the cell membrane, for cellular entry (12). From the GLUT family (13 cloned to date), GLUT4 is regulated by insulin and controls glucose uptake by skeletal muscle [which accounts for ϳ40% of total body mass (70)], cardiac muscle, and adipose tissue (75). Thus Type 1 and 2 diabetics are unable to efficiently transport glucose from the blood into these tissue groups (66) resulting in a state of hyperglycemia. Consequently, glucose inundates cells that express insulinindependent glucose transporters (such as GLUT1). Chronic elevation in cytosolic glucose leads to metabolic abnormalities such as osmotic and oxidative stress, thought to be factors that contribute to tissue injury and dysfunction associated with long-term DM (15, 61).The urinary bladder is one of th...

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“…Recently, the expression of TRPV1 has been described associated with urothelial cancers of human bladder [67]. …”

Section: Transient Receptor Potential Vanilloidmentioning

confidence: 99%

Bladder Cancer and Urothelial Impairment: The Role of TRPV1 as Potential Drug Target

Mistretta

Buffi

Lughezzani

et al. 2014

BioMed Research International

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Urothelium, in addition to its primary function of barrier, is now understood to act as a complex system of cell communication that exhibits specialized sensory properties in the regulation of physiological or pathological stimuli. Furthermore, it has been hypothesized that bladder inflammation and neoplastic cell growth, the two most representative pathological conditions of the lower urinary tract, may arise from a primary defective urothelial lining. Transient receptor potential vanilloid channel 1 (TRPV1), a receptor widely distributed in lower urinary tract structures and involved in the physiological micturition reflex, was described to have a pathophysiological role in inflammatory conditions and in the genesis and development of urothelial cancer. In our opinion new compounds, such as curcumin, the major component of turmeric Curcuma longa, reported to potentiate the effects of the chemotherapeutic agents used in the management of recurrent urothelial cancer in vitro and also identified as one of several compounds to own the vanillyl structure required to work like a TRPV1 agonist, could be thought as complementary in the clinical management of both the recurrences and the inflammatory effects caused by the endoscopic resection or intravesical chemotherapy administration or could be combined with adjuvant agents to potentiate their antitumoral effect.

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Expression of transient receptor potential vanilloid‐1 (TRPV1) in urothelial cancers of human bladder: relation to clinicopathological and molecular parameters

Cited by 46 publications

References 40 publications

Over-expression of TRPM8 is associated with poor prognosis in urothelial carcinoma of bladder

Over-expression of TRPM8 is associated with poor prognosis in urothelial carcinoma of bladder

Impact of diabetes mellitus on bladder uroepithelial cells

Bladder Cancer and Urothelial Impairment: The Role of TRPV1 as Potential Drug Target

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