scholarly journals Expression Profiles of ASIC1/2 and TRPV1/4 in Common Skin Tumors

2021 ◽  
Vol 22 (11) ◽  
pp. 6024
Author(s):  
Kirsten Ackermann ◽  
Susanne Wallner ◽  
Christoph Brochhausen ◽  
Stephan Schreml
Keyword(s):  
Cell Carcinoma ◽  
Transient Receptor Potential ◽  
Expression Profiles ◽  
Receptor Potential ◽  
Skin Tumors ◽  
Transient Receptor Potential Vanilloid ◽  
Tissue Samples ◽  
Acid Sensing Ion Channels ◽  
Common Skin ◽  
Transient Receptor

The acid-sensing ion channels ASIC1 and ASIC2, as well as the transient receptor potential vanilloid channels TRPV1 and TRPV4, are proton-gated cation channels that can be activated by low extracellular pH (pHe), which is a hallmark of the tumor microenvironment in solid tumors. However, the role of these channels in the development of skin tumors is still unclear. In this study, we investigated the expression profiles of ASIC1, ASIC2, TRPV1 and TRPV4 in malignant melanoma (MM), squamous cell carcinoma (SCC), basal cell carcinoma (BCC) and in nevus cell nevi (NCN). We conducted immunohistochemistry using paraffin-embedded tissue samples from patients and found that most skin tumors express ASIC1/2 and TRPV1/4. Striking results were that BCCs are often negative for ASIC2, while nearly all SCCs express this marker. Epidermal MM sometimes seem to lack ASIC1 in contrast to NCN. Dermal portions of MM show strong expression of TRPV1 more frequently than dermal NCN portions. Some NCN show a decreasing ASIC1/2 expression in deeper dermal tumor tissue, while MM seem to not lose ASIC1/2 in deeper dermal portions. ASIC1, ASIC2, TRPV1 and TRPV4 in skin tumors might be involved in tumor progression, thus being potential diagnostic and therapeutic targets.

scholarly journals Expression profiles of proton-sensing G-protein coupled receptors in common skin tumors

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Wybke Klatt ◽  
Susanne Wallner ◽  
Christoph Brochhausen ◽  
Judith A. Stolwijk ◽  
Stephan Schreml
Keyword(s):  
Skin Cancer ◽  
Cell Carcinoma ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Skin Tumors ◽  
Solid Cancer ◽  
Tissue Samples ◽  
Skin Cancers ◽  
Common Skin

Abstract The proton-sensing GPCRs (pH-GPCRs) GPR4 (GPR19), TDAG8 (GPR65, T-cell death associated gene 8), OGR1 (GPR68, ovarian cancer GPCR1), and G2A (GPR132, G2 accumulation protein) are involved in sensing and transducing changes in extracellular pH (pHe). Extracellular acidification is a central hallmark of solid cancer. pH-GPCR function has been associated with cancer cell proliferation, adhesion, migration and metastasis, as well as with modulation of the immune system. Little is known about the expression levels and role of pH-GPCRs in skin cancer. To better understand the functions of pH-GPCRs in skin cancer in vivo, we examined the expression-profiles of GPR4, TDAG8, OGR1 and G2A in four common skin tumors, i.e. squamous cell carcinoma (SCC), malignant melanoma (MM), compound nevus cell nevi (NCN), basal cell carcinoma (BCC). We performed immunohistochemistry and immunofluorescence staining on paraffin-embedded tissue samples acquired from patients suffering from SCC, MM, NCN or BCC. We show the expression of pH-GPCRs in four common skin cancers. Different expression patterns in the investigated skin cancer types indicate that the different pH-GPCRs may have distinct functions in tumor progression and serve as novel therapeutic targets.

scholarly journals Role of Transient Receptor Potential and Acid-sensing Ion Channels in Peripheral Inflammatory Pain

2010 ◽  
Vol 112 (3) ◽  
pp. 729-741 ◽  
Author(s):  
John P. M. White ◽  
Mario Cibelli ◽  
Antonio Rei Fidalgo ◽  
Cleoper C. Paule ◽  
Faruq Noormohamed ◽  
...  
Keyword(s):  
Ion Channels ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Ionotropic Receptors ◽  
Acid Sensing Ion Channels ◽  
Peripheral Pain ◽  
Transient Receptor

Pain originating in inflammation is the most common pathologic pain condition encountered by the anesthesiologist whether in the context of surgery, its aftermath, or in the practice of pain medicine. Inflammatory agents, released as components of the body's response to peripheral tissue damage or disease, are now known to be collectively capable of activating transient receptor potential vanilloid type 1, transient receptor potential vanilloid type 4, transient receptor potential ankyrin type 1, and acid-sensing ion channels, whereas individual agents may activate only certain of these ion channels. These ionotropic receptors serve many physiologic functions-as, indeed, do many of the inflammagens released in the inflammatory process. Here, we introduce the reader to the role of these ionotropic receptors in mediating peripheral pain in response to inflammation.

scholarly journals Properties and Differential Expression of H+ Receptors in Dorsal Root Ganglia: Is a Labeled-Line Coding for Acid Nociception Possible?

2021 ◽  
Vol 12 ◽  
Author(s):  
Omar Páez ◽  
Pedro Segura-Chama ◽  
Angélica Almanza ◽  
Francisco Pellicer ◽  
Francisco Mercado
Keyword(s):  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Transient Receptor Potential ◽  
Structural Characteristics ◽  
Expression Profiles ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Sensory Stimuli ◽  
Comparative Review ◽  
Transient Receptor

Pain by chemical irritants is one of the less well-described aspects of nociception. The acidic substance is the paradigm of the chemical noxious compound. An acidic insult on cutaneous, subcutaneous and muscle tissue results in pain sensation. Acid (or H+) has at least two main receptor channels in dorsal root ganglia (DRG) nociceptors: the heat receptor transient receptor potential vanilloid 1 (TRPV1) and the acid-sensing ionic channels (ASICs). TRPV1 is a low-sensitivity H+ receptor, whereas ASIC channels display a higher H+ sensitivity of at least one order of magnitude. In this review, we first describe the functional and structural characteristics of these and other H+-receptor candidates and the biophysics of their responses to low pH. Additionally, we compile reports of the expression of these H+-receptors (and other possible complementary proteins) within the DRG and compare these data with mRNA expression profiles from single-cell sequencing datasets for ASIC3, ASIC1, transient receptor potential Ankiryn subtype 1 (TRPA1) and TRPV1. We show that few nociceptor subpopulations (discriminated by unbiased classifications) combine acid-sensitive channels. This comparative review is presented in light of the accumulating evidence for labeled-line coding for most noxious sensory stimuli.

scholarly journals Expression profiles of TRPV1, TRPV4, TLR4 and ERK1/2 in the dorsal root ganglionic neurons of a cancer-induced neuropathy rat model

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4622 ◽  
Author(s):  
Ahmad Maqboul ◽  
Bakheet Elsadek
Keyword(s):  
Calcium Ions ◽  
Dorsal Root ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Expression Profiles ◽  
Receptor Potential ◽  
Ruthenium Red ◽  
Mechanical Hyperalgesia ◽  
Transient Receptor Potential Vanilloid ◽  
Transient Receptor

Background The spread of tumors through neural routes is common in several types of cancer in which patients suffer from a moderate-to-severe neuropathy, neural damage and a distorted quality of life. Here we aim to examine the expression profiles of transient receptor potential vanilloid 1 (TRPV1) and of transient receptor potential vanilloid 4 (TRPV4), toll-like receptor 4 (TLR4) and extracellular signal-regulated kinase (ERK1/2), and to assess the possible therapeutic strategies through blockade of transient receptor potential (TRP) channels. Methods Cancer was induced within the sciatic nerves of male Copenhagen rats, and tissues from dorsal root ganglia (DRG) were collected and used for measurements of immunofluorescence and Western blotting. The TRPV1 antagonist capsazepine, the selective TRPV4 antagonist HC-067047 and the calcium ions inhibitor ruthenium red were used to treat thermal and/or mechanical hyperalgesia. Results Transient receptor potential vanilloid 1 showed a lower expression in DRGs on days 7 and 14. The expression of TRPV4, TLR4 and ERK1/2 showed an increase on day 3 then a decrease on days 7 and 14. TRPV1 and TLR4 as well as TRPV4 and ERK1/2 co-existed on the same neuronal cells. The neuropathic pain was reversed in dose-dependent manners by using the TRP antagonists and the calcium ions inhibitor. Conclusion The decreased expression of TRPV1 and TRPV4 is associated with high activation. The increased expression of TLR4 and ERK1/2 reveals earlier immune response and tumor progression, respectively, and their ultimate decrease is an indicator of nerve damage. We studied the possible role of TRPV1 and TRPV4 in transducing cancer-induced hyperalgesia. The possible treatment strategies of cancer-induced thermal and/or mechanical hyperalgesia using capsazepine, HC-067047 and ruthenium red are examined.

scholarly journals Evolution of acid nociception: ion channels and receptors for detecting acid

2019 ◽  
Vol 374 (1785) ◽  
pp. 20190291 ◽  
Author(s):  
Luke A. Pattison ◽  
Gerard Callejo ◽  
Ewan St John Smith
Keyword(s):  
Ion Channels ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
G Protein Coupled Receptors ◽  
Transient Receptor Potential Vanilloid ◽  
Ionic Homeostasis ◽  
Acid Sensing Ion Channels ◽  
Transient Receptor ◽  
G Protein Coupled ◽  
Cold Pressure

Nociceptors, i.e. sensory neurons tuned to detect noxious stimuli, are found in numerous phyla of the Animalia kingdom and are often polymodal, responding to a variety of stimuli, e.g. heat, cold, pressure and chemicals, such as acid. Owing to the ability of protons to have a profound effect on ionic homeostasis and damage macromolecular structures, it is no wonder that the ability to detect acid is conserved across many species. To detect changes in pH, nociceptors are equipped with an assortment of different acid sensors, some of which can detect mild changes in pH, such as the acid-sensing ion channels, proton-sensing G protein-coupled receptors and several two-pore potassium channels, whereas others, such as the transient receptor potential vanilloid 1 ion channel, require larger shifts in pH. This review will discuss the evolution of acid sensation and the different mechanisms by which nociceptors can detect acid. This article is part of the Theo Murphy meeting issue ‘Evolution of mechanisms and behaviour important for pain’.

Sign in / Sign up

Export Citation Format

Share Document