Expression of the transient receptor potential vanilloid 1 (TRPV1) in LNCaP and PC-3 prostate cancer cells and in human prostate tissue

Sánchez, María del Mar; Sánchez, Ana M.; Collado, Beatriz; Malagarie‐Cazenave, Sophie; Olea, Nuria; Carmena, Marı́a J.; Prieto, Juan Carlos; Díaz‐Laviada, Inés

doi:10.1016/j.ejphar.2005.04.010

Cited by 125 publications

(101 citation statements)

References 37 publications

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“…The significance of TRPV1 expression in prostate carcinoma cells (Sanchez et al, 2005) is unclear since the TRPV1 agonist capsaicin was reported to stimulate the growth of androgen-responsive cancer cells derived from lymph node metastasis of prostate carcinoma (Malagarie-Cazenave et al, 2009), a most puzzling observation since TRPV1 agonism is usually advocated to kill TRPV1-expressing cancerous cells. Indeed, capsaicin induces apoptosis in the PC-3 prostate cancer cell line (Sánchez et al, 2006).…”

Section: G Transient Receptor Potential Channels In Cancermentioning

confidence: 99%

Transient Receptor Potential Channels as Drug Targets: From the Science of Basic Research to the Art of Medicine

2014

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Section: G Transient Receptor Potential Channels In Cancermentioning

confidence: 99%

Transient Receptor Potential Channels as Drug Targets: From the Science of Basic Research to the Art of Medicine

2014

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“…Epithelial cells control their cytosolic Ca 2ϩ level via non-voltage-gated plasma membrane cationic channels and/or depletion of intracellular Ca 2ϩ stores followed by Ca 2ϩ entry via store-operated channels. Several plasma membrane channels have been implicated in modulation of cytosolic Ca 2ϩ in prostate epithelial cells (2)(3)(4)(5)(6). Notably, the two highly Ca 2ϩ -selective Ca 2ϩ (re)absorption channels TRPV5 3 and TRPV6 were found to be expressed in prostate cells (7)(8)(9).…”

Section: Camentioning

confidence: 99%

G Protein-coupled Receptor Signaling via Src Kinase Induces Endogenous Human Transient Receptor Potential Vanilloid Type 6 (TRPV6) Channel Activation

Spehr

Gelis

Osterloh

et al. 2011

Journal of Biological Chemistry

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Ca2؉ homeostasis plays a critical role in a variety of cellular processes. We showed previously that stimulation of the prostate-specific G protein-coupled receptor (PSGR) enhances cytosolic Ca 2؉ and inhibits proliferation of prostate cells. Here, we analyzed the signaling mechanisms underlying the PSGR-mediated Ca 2؉ increase. Using complementary molecular, biochemical, electrophysiological, and live-cell imaging techniques, we found that endogenous Ca 2؉ -selective transient receptor potential vanilloid type 6 (TRPV6) channels are critically involved in the PSGR-induced Ca 2؉ signal. Biophysical characterization of the current activated by PSGR stimulation revealed characteristic properties of TRPV6. The molecular identity of the involved channel was confirmed using RNA interference targeting TrpV6. TRPV6-mediated Ca 2؉ influx depended on Src kinase activity. Src kinase activation occurred independently of G protein activation, presumably by direct interaction with PSGR. Taken together, we report that endogenous TRPV6 channels are activated downstream of a G protein-coupled receptor and present the first physiological characterization of these channels in situ. Ca2ϩ ions function as ubiquitous second messengers that control a variety of cellular processes such as differentiation, proliferation, and apoptosis (1). Epithelial cells control their cytosolic Ca 2ϩ level via non-voltage-gated plasma membrane cationic channels and/or depletion of intracellular Ca 2ϩ stores followed by Ca 2ϩ entry via store-operated channels. Several plasma membrane channels have been implicated in modulation of cytosolic Ca 2ϩ in prostate epithelial cells (2-6). Notably, the two highly Ca 2ϩ -selective Ca 2ϩ (re)absorption channels TRPV5 3 and TRPV6 were found to be expressed in prostate cells (7-9). TRPV6 has been proposed to play a role in prostate cancer cell proliferation (9, 10). The biophysical characteristics of recombinantly overexpressed TRPV6 channels have been studied intensively (11). However, no information on channel physiology in native cells is available. Overexpression of TRPV6 leads to constitutively open channels, and so far no activation mechanism has been described (12). We previously reported that activation of PSGR by ␤-ionone induces an increase in cytosolic Ca 2ϩ and a decreased proliferation rate of prostate cancer cells (13). Thus, the aim of the present study was to examine the mechanism of Ca 2ϩ entry into prostate epithelial cells upon stimulation of PSGR, a class A GPCR that was initially identified as a prostate-specific tumor biomarker (14). Here, we identified TRPV6 as an important signaling protein downstream of activated PSGR showing that TRPV6 can function as a receptor-operated channel. We further identified the tyrosine kinase Src as a signaling protein coupling PSGR and TRPV6 independently of G proteins. In this context, we present the first electrophysiological analysis of endogenous TRPV6 channels. EXPERIMENTAL PROCEDURESCell Culture and Transfection-LNCaP cells were maintained in RPMI 1640...

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“…Also in addition to the TRPCs, which have been implicated in forming MscCa, other TRP subfamily members are expressed in tumor cells and have been implicated in diVerent steps associated with cancer (Peng et al, 2001;Wissenbach et al, 2001;Nilius et al, 2005;Sánchez et al, 2005). Of particular interest is TRPM7 that has been shown to regulate cell adhesion by regulating calpain via Ca 2þ influx through the channel (Su et al, 2006) and actomyosin contractility via intrinsic kinase activity of TRPM7 (Clark et al, 2006).…”

Section: Mscca and Metastasismentioning

confidence: 99%

The Mechanosensitive Ca2+ Channel as a Central Regular of Prostate Tumor Cell Migration and Invasiveness

Hamill¹

2011

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. REPORT DATE (DD-MM-YYYY)2. REPORT TYPE 3. DATES COVERED (From -To) 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e. TASK NUMBER E-Mail:5f. WORK UNIT NUMBER 4 Introduction A major challenge for treating prostate cancer (PC) is to discover new therapies that will prevent the spread of PC cells from the prostate to distal sites. Our research focuses on the stretch-activated mechanosensitive Ca 2+ permeant channel (MscCa) as a central regulator of prostate tumor cell migration. Our experiments are designed to address the two most basic issues of the disease: the mechanism(s) that trigger progression of PC to malignancy and the urgent need for new therapeutic targets to block or reverse this progression. Our original experiments funded by DOD were aimed to test whether MscCa is expressed in human prostate tumor cells and whether MscCa activity is required for prostate tumor cell migration. We confirmed both results. In the course of these experiments we also discovered that the predominate gating mode of the MscCa differs between noninvasive and invasive PC cells, may be the most powerful determinate of the [Ca 2+ ]i dynamics required to coordinate cell locomotion. The aims of the current award were three-fold. First, determine the mechanisms underlying MscCa gating. Second, determine the cancer-related processes that switch MscCa gating, and third determine whether anti-MscCa conditions that suppress PC migration in vitro also block PC cell invasion in vivo. Insights into these aspects would provide added motivation for developing more selective therapies that target MscCa and its regulatory mechanisms. The basic results supporting our hypothesis have been published (Maroto, R. & Hamill, O.P. MscCa regulation of tumor cell migration and metastasis. Current Topics in Membranes.59, 485-509, 2007). Also included in the Appendix are other manuscripts and abstracts Gotlieb et al., 2008; Maroto & Hamill, 2011; and Maroto, Kurosky and Hamill, 2011) that include specific results described in body of the text. PERFORMING ORGANIZATION NAME(S) AND AD...

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Expression of the transient receptor potential vanilloid 1 (TRPV1) in LNCaP and PC-3 prostate cancer cells and in human prostate tissue

Cited by 125 publications

References 37 publications

Transient Receptor Potential Channels as Drug Targets: From the Science of Basic Research to the Art of Medicine

Transient Receptor Potential Channels as Drug Targets: From the Science of Basic Research to the Art of Medicine

G Protein-coupled Receptor Signaling via Src Kinase Induces Endogenous Human Transient Receptor Potential Vanilloid Type 6 (TRPV6) Channel Activation

The Mechanosensitive Ca2+ Channel as a Central Regular of Prostate Tumor Cell Migration and Invasiveness

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