Expression of Bioactive Chemerin by Keratinocytes Inhibits Late Stages of Tumor Development in a Chemical Model of Skin Carcinogenesis

Chemerin is a multifunctional protein acting mainly through the G protein-coupled receptor ChemR23/CMKLR1/Chemerin1. Its expression is frequently downregulated in human tumors, including in melanoma and squamous cell carcinoma of the skin and anti-tumoral properties of chemerin were reported in mouse tumor graft models. In the present study, we report the development of spontaneous skin tumors in aged ChemR23-deficient mice. In order to test the potential therapeutic benefit of chemerin analogs, a transgenic model in which bioactive chemerin is over-expressed by basal keratinocytes was generated. These animals are characterized by increased levels of chemerin immunoreactivity and bioactivity in the skin and the circulation. In a chemical carcinogenesis model, papillomas developed later, were less numerous, and their progression to carcinomas was delayed. Temporal control of chemerin expression by doxycycline allowed to attribute its effects to late stages of carcinogenesis. The protective effects of chemerin were partly abrogated by ChemR23 invalidation. These results demonstrate that chemerin is able to delay very significantly tumor progression in a model that recapitulates closely the evolution of solid cancer types in human and suggest that the chemerin-ChemR23 system might constitute an interesting target for therapeutic intervention in the cancer field.
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research

Related Links:

Abstract Skin substitutes have shown success in complex wound reconstruction. We evaluate the use of a human acellular dermal matrix (ADM) as a viable alternative to autologous skin grafting for defects secondary to skin cancer excision. An institutional review board-approved, retrospective review of ADM-reconstructed defects secondary to skin cancer excision between 2012 and 2018 was conducted. ADM was indicated in patients with preclusive factors for general anesthesia, protracted procedure time, reluctance for additional donor site wound, and personal choice. We reviewed defect characteristics, healing time, po...
Source: The American Surgeon - Category: Surgery Authors: Tags: Am Surg Source Type: research
ConclusionsThis study brings out consequential information on factors linked with invaded or insufficient excision margins. Larger cohorts should evaluate the aesthetic outcomes in such a population.
Source: Journal of Cranio Maxillofacial Surgery - Category: ENT & OMF Source Type: research
ConclusionHealth professionals must consider this pathology when evaluating a burn scar or a chronic wound, performing a biopsy when suspicion is high. An early diagnosis, a prompt surgical intervention and a greater vigilance are the keys to success and survival.
Source: International Journal of Surgery Case Reports - Category: Surgery Source Type: research
Discussion MDSCs violently emerge in pathological conditions in an attempt to limit potentially harmful immune and inflammatory responses. Mechanisms supporting their expansion and survival are deeply investigated in cancer, in the perspective to reactivate specific antitumor responses and prevent their contribution to disease evolution. These findings will likely contribute to improve the targeting of MDSCs in anticancer immunotherapies, either alone or in combination with immune checkpoint inhibitors. New evidence indicates that the expansion of myeloid cell differentiation in pathology is subject to fine-tuning, as its...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusions Lymphatic vessels, like blood vessels, are a highly interactive surface for cells of the immune system, and through the use of chemokines and their receptors can coordinate key interactions. These pathways can control the entry and function of particular immune subsets in a number of pathological conditions. Nonetheless LECs have distinct patterns of chemokine secretion and expression of chemokine receptors that distinguish them from the blood vessel system and mediate distinct roles and responses. The abundance and diversity of the chemokine family point to the likelihood that a plethora of novel chemokine fu...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Discussion Suppressor of cytokine signaling 1 is an essential molecule for maintaining immune homeostasis and subverting inflammation. Disorders arising from excess inflammation or SOCS1 deficiency can be potentially treated with SOCS1 mimetics (Ahmed et al., 2015). While SOCS1 has promising potential in many disorders, it should be noted that new targets and actions of SOCS1 are still being discovered and not all the effects of this protein are beneficial in autoimmune diseases and cancer. For instance, SOCS1 degrades IRS1 and IRS2, required for insulin signaling, via the SOCS Box domain, thus, limiting its potential in ...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Publication date: Available online 13 September 2018Source: British Journal of Oral and Maxillofacial SurgeryAuthor(s): A.J. Dalal, J. Ingham, B. Collard, G. MerrickAbstractWe provide a non-melanoma skin cancer (NMSC) service for skin cancers of the head and neck in the south-west of England. We hypothesised that certain anatomical sites such as the nose and eyelid would have a higher incidence of close or involved margins than others, and that the choice of repair might influence the excised margins. We therefore retrospectively analysed the data of 500 consecutive NMSC that were operated on in the oral and maxillofacial ...
Source: British Journal of Oral and Maxillofacial Surgery - Category: ENT & OMF Source Type: research
Cutaneous Squamous cell carcinoma (cSCC) is after basal cell carcinoma the second most common non-melanoma skin cancer and accounts for 20% of all cutaneous malignancies [1]. Particularly effected are organ transplant recipients (OTRs) with a 65 to 250 higher risk than the general population due to their immunosuppression as major risk factor [2]. Moreover, cSCC in OTRs are often quite aggressive with high recurrence rates, metastasis and death [3]. The most widely used agents to prevent graft rejection in solid OTRs are calcineurin-inhibitors in combination with mycophenolate mofetil (MMF) and corticosteroids as the stand...
Source: Journal of Dermatological Science - Category: Dermatology Authors: Source Type: research
CONCLUSIONS:Biopsies are warranted for any VLU with documented stalled healing following 3 months of standard of care. One biopsy is performed at the periphery of the ulcer and another at the base in order to rule out the presence of malignant transformation because of BCC, squamous cell carcinoma, sarcoma, melanoma, lymphoma, or metastases. BACKGROUND: Nonmelanoma skin cancers rarely arise from venous leg ulcers (VLUs). Although basal cell carcinoma (BCC) is the most common nonmelanoma skin cancer, its association with lower-extremity ulcers is not as frequently reported as other malignancies. OBJECTIVE: To report ...
Source: Advances in Skin and Wound Care - Category: Dermatology Tags: Features: Case Series Source Type: research
Abstract: Background: Immunosuppressive therapy, which is necessary to avoid graft rejection in renal transplant recipients, presents an increased risk of several pathologies, namely infectious and neoplastic. Objectives: To identify the most frequent skin diseases and their clinical and demographical risk factors within a population of renal transplant recipients. Methods: A retrospective study of renal transplant recipients referred to dermatology visit and observed for the first time from January 2008 to December 2014. Results: The study included 197 patients, 120 men (60,9%). Mean age was 50,7 years ( ±13,4). 12...
Source: Anais Brasileiros de Dermatologia - Category: Dermatology Source Type: research
More News: Cancer | Cancer & Oncology | Carcinoma | Chemistry | Doxycycline | Melanoma | Skin | Skin Cancer | Skin Graft | Squamous Cell Carcinoma | Study