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

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.

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Expression of Proton-Sensitive GPR31, GPR151, TASK1 and TASK3 in Common Skin Tumors

Cells ◽

10.3390/cells11010027 ◽

2021 ◽

Vol 11 (1) ◽

pp. 27

Author(s):

Antonia Förch ◽

Susanne Wallner ◽

Florian Zeman ◽

Tobias Ettl ◽

Christoph Brochhausen ◽

...

Keyword(s):

Expression Profiles ◽

Expression Patterns ◽

Skin Tumors ◽

Tissue Samples ◽

Basal Cell Carcinomas ◽

Common Skin ◽

G Protein Coupled ◽

Nevus Cell ◽

Lower Expression

TWIK-related acid-sensitive potassium channels TASK1 and TASK3, as well as the G-protein-coupled receptors GPR31 and GPR151, are proton-sensitive membrane proteins. They can be activated or inhibited 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 TASK1, TASK3, GPR31 and GPR151 in squamous cell carcinomas (SCCs), basal cell carcinomas (BCCs), nevus cell nevi (NCN), and malignant melanomas (MMs). We performed immunohistochemistry using paraffin-embedded tissue samples from patients and found that most skin tumors express TASK1/3 and GPR31/151. The results show that BCCs are often negative for GPR31/151 as well as for TASK1/3, while nearly all SCCs express these markers. MMs and NCN show similar expression patterns. However, some tumors show a decreasing TASK1/3 expression in deeper dermal tumor tissue, while GPCRs were expressed more evenly. The lower frequency of GPR31/151 and TSAK1/3 expression in BCCs when compared to SCCs is a novel histological feature distinguishing these two entities. Moreover, BCCs also show lower expression of GPR31/151 and TASK1/3 as compared to NCN and MMs.

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

International Journal of Molecular Sciences ◽

10.3390/ijms22116024 ◽

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.

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Circular RNA circSDHC serves as a sponge for miR-127-3p to promote the proliferation and metastasis of renal cell carcinoma via the CDKN3/E2F1 axis

Molecular Cancer ◽

10.1186/s12943-021-01314-w ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Junjie Cen ◽

Yanping Liang ◽

Yong Huang ◽

Yihui Pan ◽

Guannan Shu ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Target Genes ◽

Expression Patterns ◽

Luciferase Reporter ◽

Circular Rnas ◽

Proliferation And Metastasis

Abstract Background There is increasing evidence that circular RNAs (circRNAs) have significant regulatory roles in cancer development and progression; however, the expression patterns and biological functions of circRNAs in renal cell carcinoma (RCC) remain largely elusive. Method Bioinformatics methods were applied to screen for circRNAs differentially expressed in RCC. Analysis of online circRNAs microarray datasets and our own patient cohort indicated that circSDHC (hsa_circ_0015004) had a potential oncogenic role in RCC. Subsequently, circSDHC expression was measured in RCC tissues and cell lines by qPCR assay, and the prognostic value of circSDHC evaluated. Further, a series of functional in vitro and in vivo experiments were conducted to assess the effects of circSDHC on RCC proliferation and metastasis. RNA pull-down assay, luciferase reporter and fluorescent in situ hybridization assays were used to confirm the interactions between circSDHC, miR-127-3p and its target genes. Results Clinically, high circSDHC expression was correlated with advanced TNM stage and poor survival in patients with RCC. Further, circSDHC promoted tumor cell proliferation and invasion, both in vivo and in vitro. Analysis of the mechanism underlying the effects of circSDHC in RCC demonstrated that it binds competitively to miR-127-3p and prevents its suppression of a downstream gene, CDKN3, and the E2F1 pathway, thereby leading to RCC malignant progression. Furthermore, knockdown of circSDHC caused decreased CDKN3 expression and E2F1 pathway inhibition, which could be rescued by treatment with an miR-127-3p inhibitor. Conclusion Our data indicates, for the first time, an essential role for the circSDHC/miR-127-3p/CDKN3/E2F1 axis in RCC progression. Thus, circSDHC has potential to be a new therapeutic target in patients with RCC.

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Detailed head localization and incidence of skin cancers

Scientific Reports ◽

10.1038/s41598-021-91942-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Marta Fijałkowska ◽

Mateusz Koziej ◽

Bogusław Antoszewski

Keyword(s):

Skin Cancer ◽

Cell Carcinoma ◽

Vertical Dimension ◽

Surgical Department ◽

Surface Areas ◽

Common Cancer ◽

Skin Cancers ◽

Sex Type ◽

Cancer Subtype ◽

The Face

AbstractSkin cancers are the most common neoplasms; frequently, they localize on the face. The aim of paper is to present the incidence of skin tumors in a single center from 2017 to 2019, describe trends in its frequency and find relations between neoplasms and sex, type of cancer, and its size. An analysis of histopathological files from the surgical department between 2017 and 2019 was calculated. These items were selected: sex, age, type of skin cancer, subtype of basal cell carcinoma (BCC), grading of squamous cell carcinoma (SCC), localization and dimensions of the tumor. The study sample consisted of 387 cases. BCC was the most common cancer and its nodular type was the most frequent. In older patients, the vertical dimension of excised carcinoma was significantly larger. Moreover, this connection was detected only in women compared to men. There were statistically significant differences between dimensions of the skin cancer and sex. In men group, skin cancers had statistically higher vertical dimensions and larger surface areas. On the face and head, BCC more often localizes in the nasal area, while SCC on the auricle. It has been demonstrated that the older the patient, the larger the vertical dimension of the tumor. As such, tumor size is larger in men than in women, as women usually see their physicians sooner than men: cosmetic concerns are more important to them.

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Photosensitizing Medications and Skin Cancer: A Comprehensive Review

Cancers ◽

10.3390/cancers13102344 ◽

2021 ◽

Vol 13 (10) ◽

pp. 2344

Author(s):

Elisabeth A. George ◽

Navya Baranwal ◽

Jae H. Kang ◽

Abrar A. Qureshi ◽

Aaron M. Drucker ◽

...

Keyword(s):

Skin Cancer ◽

Cancer Risk ◽

Cell Carcinoma ◽

The United States ◽

In Vivo Studies ◽

Cancer Risk Factors ◽

Skin Cancer Risk ◽

Number Of Patients

(1) The incidence of skin cancer is increasing in the United States (US) despite scientific advances in our understanding of skin cancer risk factors and treatments. In vitro and in vivo studies have provided evidence that suggests that certain photosensitizing medications (PSMs) increase skin cancer risk. This review summarizes current epidemiological evidence on the association between common PSMs and skin cancer. (2) A comprehensive literature search was conducted to identify meta-analyses, observational studies and clinical trials that report on skin cancer events in PSM users. The associated risks of keratinocyte carcinoma (squamous cell carcinoma and basal cell carcinoma) and melanoma are summarized, for each PSM. (3) There are extensive reports on antihypertensives and statins relative to other PSMs, with positive and null findings, respectively. Fewer studies have explored amiodarone, metformin, antimicrobials and vemurafenib. No studies report on the individual skin cancer risks in glyburide, naproxen, piroxicam, chlorpromazine, thioridazine and nalidixic acid users. (4) The research gaps in understanding the relationship between PSMs and skin cancer outlined in this review should be prioritized because the US population is aging. Thus the number of patients prescribed PSMs is likely to continue to rise.

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Skin Cancers and the Contribution of Rho GTPase Signaling Networks to Their Progression

Cancers ◽

10.3390/cancers13174362 ◽

2021 ◽

Vol 13 (17) ◽

pp. 4362

Author(s):

Alessandra Pecora ◽

Justine Laprise ◽

Manel Dahmene ◽

Mélanie Laurin

Keyword(s):

Skin Cancer ◽

Cell Carcinoma ◽

Cancer Biology ◽

Rho Gtpase ◽

Signaling Networks ◽

Molecular Events ◽

Skin Cancers ◽

Cancer Initiation ◽

Cytoskeletal Dynamics ◽

Genetic Perturbations

Skin cancers are the most common cancers worldwide. Among them, melanoma, basal cell carcinoma of the skin and cutaneous squamous cell carcinoma are the three major subtypes. These cancers are characterized by different genetic perturbations even though they are similarly caused by a lifelong exposure to the sun. The main oncogenic drivers of skin cancer initiation have been known for a while, yet it remains unclear what are the molecular events that mediate their oncogenic functions and that contribute to their progression. Moreover, patients with aggressive skin cancers have been known to develop resistance to currently available treatment, which is urging us to identify new therapeutic opportunities based on a better understanding of skin cancer biology. More recently, the contribution of cytoskeletal dynamics and Rho GTPase signaling networks to the progression of skin cancers has been highlighted by several studies. In this review, we underline the various perturbations in the activity and regulation of Rho GTPase network components that contribute to skin cancer development, and we explore the emerging therapeutic opportunities that are surfacing from these studies.

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Surgical Management of Melanoma and Other Skin Cancers

10.2310/surg.2038 ◽

2015 ◽

Author(s):

Jennifer A. Wargo ◽

Kenneth Tenabe

Keyword(s):

Lymph Node ◽

Surgical Treatment ◽

Skin Cancer ◽

Cell Carcinoma ◽

Stage Iv ◽

Stage Iii ◽

Non Melanoma Skin Cancer ◽

Skin Cancers ◽

Stage Iv Melanoma ◽

Melanoma Skin

The prevalence of malignant skin cancers has increased significantly over the past several years. Approximately 1.2 million cases of non-melanoma skin cancer are diagnosed per year. More alarming, up to 80,000 cases of melanoma are diagnosed per year, an incidence that has been steadily increasing, with a lifetime risk of 1 in 50 for the development of melanoma. The disturbing increase in the incidence of both non-melanoma skin cancer and melanoma can largely be attributed to the social attitude toward sun exposure. The clinical assessment and management of skin lesions can be challenging. This review describes the assessment process, including thorough history and examination; the need for possible biopsy; and excision criteria. Specific types of skin cancer are distinguished and include basal cell carcinoma; squamous cell carcinoma; and melanoma; and for each type the incidence; epidemiology; histologic subtypes; diagnosis; and both surgical and non-surgical treatments are provided. Stages I-IV of melanoma are detailed, with prognostic factors described. Surgical treatment for stages I and II include description of the margins of excision and sentinel lymph node biopsy. The surgical treatment of Stage III melanoma further includes therapeutic lymph node dissection and isolated limb perfusion. Adjuvant therapies are also presented and include radiotherapy and chemotherapy. The additional treatment of metastasectomy for Stage IV melanoma is described. For both Stage III and IV melanoma, the study of vaccines to host immune cells is reported. For Stage IV melanoma, the text also describes immunotherapy treatment. Operative procedures specific to superficial and deep groin dissections are outlined. This review contains 9 figures, 3 tables, and 96 references.

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258. Differential expression of H2A and H3 variant histones in mouse preimplantation embryos and R1 ES cells

Reproduction Fertility and Development ◽

10.1071/srb08abs258 ◽

2008 ◽

Vol 20 (9) ◽

pp. 58

Author(s):

G. R. Kafer ◽

SA Lehnert ◽

P. L. Kaye ◽

R. J. Moser

Keyword(s):

Messenger Rna ◽

Expression Profiles ◽

Es Cells ◽

Expression Patterns ◽

Embryonic Stem ◽

Histone Variants ◽

Histone Variant ◽

Preimplantation Embryos ◽

Es Cell

Histone variants replace canonical histones in nucleosomes to serve numerous biological processes. This integration alters DNA properties to ultimately regulate gene expression. Previous mouse studies have indicated that some variants (H2AZ and H3.3) are essential for survival, but here we document and correlate histone expression patterns with key developmental events. Using quantitative reverse-transcribed PCR (qRT–PCR) we investigated the expression of 7 genes coding for H2A variants and 4 genes coding for H3 variants in mouse preimplantation embryos and in pluripotent R1 ES cells. Messenger RNA was extracted from pools of 3 embryos flushed from superovulated mice. Embryos were collected at five stages, zygotes, 2-cell embryos, morulae, blastocysts and hatching blastocysts (20 h, 44 h, 68 h, 92 h and 116 h post hCG respectively). The expression of H2A variant genes typically peaked within blastocysts. H2AZ and H2AX expression was 80 – 95% higher in blastocysts than other stages. Conversely, genes coding for H3 variants showed elevated expression in zygotes, where H3.3 expression was 85 – 95% higher and CENPA was ~75% higher than in later preimplantation stages. The expression profiles of histone remodellers SWI/SNF and CAF-1 correlated with the variants they are known to remodel (H2A and H3 variants respectively), suggesting an increased integration of those variants into nucleosomes. We also compared blastocyst and embryonic stem cell (ES cell) expression patterns. R1 ES cells express all histone variants, including H2A.Bbd, H3.1 and H3.2 which were not expressed in preimplantation embryos. Further, expression levels of every histone variant investigated differed significantly between R1 ES cells and hatching blastocysts (ANOVA, P < 0.05, n = 3 experiments). We conclude that histone variant expression reflects preimplantation developmental demands. Further, histone code expression profiles show significant change upon extended cell culture and maintenance of pluripotency as indicated by comparing in vivo hatching blastocysts to the R1 ES cell line.

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A rare case of intracranial malignant melanoma with an unusual presentation

Asian Journal of Medical Sciences ◽

10.3126/ajms.v7i6.15201 ◽

2016 ◽

Vol 7 (6) ◽

pp. 91-93

Author(s):

Sandeep B V ◽

Suniti Kumar Saha ◽

Manpreet Singh Banga ◽

Partha Ghosh

Keyword(s):

Skin Cancer ◽

Malignant Melanoma ◽

Head And Neck ◽

Rare Case ◽

Medical Sciences ◽

Skin Cancers ◽

Common Skin ◽

The Common ◽

Sixth Decade ◽

Geographical Locations

Among the common skin cancers, melanoma is the most lethal. Although, it comprises only 3% of all skin cancers diagnosed , it accounts for about 75% of all skin cancer-related deaths. Melanoma is a relatively uncommon skin cancer in geographical locations like India. Its highest incidence is seen in sixth decade . Head and neck melanomas constitute approximately 17% of all cutaneous melanomas .We present a 15 year old male patient who presented with a intracranial melanoma with osteolytic skull lesion.Asian Journal of Medical Sciences Vol.7(5) 2016 91-93

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40-Year Trends in Skin Cancer in British Columbia, Canada, 1973 to 2003

Journal of Cutaneous Medicine and Surgery ◽

10.2310/7750.2011.11001 ◽

2012 ◽

Vol 16 (2) ◽

pp. 83-91 ◽

Cited By ~ 11

Author(s):

David I. Mclean ◽

Norm Phillips ◽

Youwen Zhou ◽

Richard Gallagher ◽

Tim K. Lee

Keyword(s):

British Columbia ◽

Skin Cancer ◽

Cell Carcinoma ◽

Incidence Rate ◽

Incidence Rates ◽

Cutaneous Malignant Melanoma ◽

Skin Cancers ◽

Canadian Population ◽

Novel Method ◽

Over Time

Background: Skin cancer is common in North America. Incidence rate trends are potentially important in the assessment of the effects of measures to increase sun awareness in the population as well as measures to reduce sun damage. Objective: To determine the incidence of basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and cutaneous malignant melanoma (CMM) in a geographically defined Canadian population over a 40-year period. Methods: Data were obtained from the BC Cancer Registry for the calendar years 1973, 1983, 1993, and 2003. Results: Age-standardized incidence rates increased significantly from 1973 to 2003 for BCC, SCC, and CMM. Limitations: The ethnic makeup of British Columbia has changed over time, and a novel method of accounting for the effect of this on skin cancer rates is presented. Conclusion: The incidence rate for skin cancers continued to rise in British Columbia, but there appears to have been a decline in the incidence of CMM and BCC in the youngest cohorts.

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