Dermal Cell News Volume 4.18 | May 28 2018

TOP STORY

Multicolor Lineage Tracing Reveals Clonal Dynamics of Squamous Carcinoma Evolution from Initiation to Metastasis

Researchers analyzed the clonal evolution of squamous skin carcinomas induced by DMBA/TPA treatment using the K5CreER-Confetti mouse and stage-specific lineage tracing. Newly generated clones within carcinomas demonstrate intratumoral invasion and clonal intermixing, often giving rise to metastases containing two or more distinct clones derived from the matched primary tumor. [Nat Cell Biol] Abstract

(Ranked by impact factor of the journal)

DERMAL STEM CELLS & TISSUE REGENERATION

β-Catenin Activation in Hair Follicle Dermal Stem Cells Induces Ectopic Hair Outgrowth and Skin Fibrosis

Investigators report that activation of β-catenin in dermal sheath (DS) generated ectopic HF outgrowth by reprogramming HF epidermal cells and DS cells themselves, and endowed DS cells with hair inducing ability. Epidermal homeostasis of pre-existing HFs was disrupted. Additionally, cell-autonomous progressive skin fibrosis was prominent in dermis, where the excessive fibroblasts largely originate from DS. [J Mol Cell Biol] Abstract

Epidermal HMGB1 Activates Dermal Fibroblasts and Causes Hypertrophic Scar Formation in Reduced Hydration

High-mobility group box 1 (HMGB1) was detected in the nuclei of epidermal cells in normal skin and had accumulated in the cytoplasm in hypertrophic scars. By establishing a keratinocyte-fibroblast co-culture and conditional medium treatment models, scientists found that a reduced hydration condition increased the expression and secretion of HMGB1 in keratinocytes, subsequently activating dermal fibroblasts. [J Invest Dermatol] Abstract

Vitamin D Receptor Is Required for Proliferation, Migration and Differentiation of Epidermal Stem Cells and Progeny during Cutaneous Wound Repair

The requirement for vitamin D receptor (VDR) on epidermal stem cell function was revealed in conditional VDR knockout mice, in which VDR was deleted from stem cells and progeny, and mice were maintained on a low calcium diet. Wound induced migration of stem cells and progeny was impaired as shown by lineage tracing and delayed migration of VDR silenced cells. [J Invest Dermatol] Abstract

Epidermal Glucocorticoid and Mineralocorticoid Receptors Act Cooperatively to Regulate Epidermal Development and Counteract Skin Inflammation

Immortalized double knockout (DKO) keratinocytes featured increased proliferation kinetics and reduced cell size, a unique phenotype relative to single KO cells. The lack of glucocorticoid receptor and mineralocorticoid receptor in keratinocytes, individual or combined, caused constitutive increases in p38 and ERK activities, which were partially reversed upon reinsertion of receptors into DKO cells. [Cell Death Dis] Full Article

Oxyfadichalcone C Inhibits Melanoma A375 Cell Proliferation and Metastasis via Suppressing PI3K/Akt and MAPK/ERK Pathways

Oxyfadichalcone C potently inhibited proliferation, induced G1 phase arrest and weak apoptosis in A375 cells. Anti-migration and anti-invasion activities were also indicated. Such effects were associated with upregulation of p27, reduction of cyclin D1, p-pRb, p-Integrin β1, as well as the proteolytic activity of metalloproteinase-2/9. [Life Sci] Abstract

SKIN CANCERS & DISORDERS

Targeting the Upstream Transcriptional Activator of PD-L1 as an Alternative Strategy in Melanoma Therapy

Scientists demonstrated that ultraviolet radiation induction of programmed cell death ligand 1 (PD-L1) in skin is directly controlled by nuclear factor E2-related transcription factor 2 (NRF2). Depletion of NRF2 significantly induced tumor infiltration by both CD8⁺ and CD4⁺ T cells to suppress melanoma progression, and combining NRF2 inhibition with anti-PD-1 treatment enhanced its anti-tumor function. [Oncogene] Abstract

Comparison of Direct and Indirect Cold Atmospheric-Pressure Plasma Methods in the B₁₆F₁₀ Melanoma Cancer Cells Treatment

Researchers implemented and investigated a novel method to destroy cancer cells inside the mouse body on a clinical level. In the case of the in vitro study, MTT assay were employed to discover an effective dose of applied plasma and distinguish the plasma effect in direct and in indirect treatments. Tumor growth was also measured in vivo so that the effectiveness of direct and indirect treatments could be compared. [Sci Rep] Full Article

Aberrant Modulation of Ribosomal Protein S6 Phosphorylation Confers Acquired Resistance to MAPK Pathway Inhibitors in BRAF-Mutant Melanoma

In resistant cells (A375-DR and A375-TR), phosphorylation of ribosomal protein S6 (rpS6) but not phosphorylation of ERK or p90 ribosomal S6 kinase were unable to be inhibited by MAPK pathway inhibitors. Knockdown of rpS6 in these cells effectively downregulated G1 phase-related proteins, including RB, cyclin D1, and CDK6, induced cell cycle arrest, and inhibited proliferation, suggesting that aberrant modulation of rpS6 phosphorylation contributed to the acquired resistance. [Acta Pharmacol Sin] Abstract

LncRNA MEG3 Repressed Malignant Melanoma Progression via Inactivating Wnt Signaling Pathway

Investigators found that overexpression of MEG3 was able to inhibit cell proliferation and colony formation capacity. It was indicated that Wnt signaling was highly activated in melanoma cells with β‐catenin expression significantly increased and GSK‐3β decreased. MEG restoration strongly inactivated Wnt signaling pathway by reducing β‐catenin and CyclinD1, elevating GSK‐3β levels in vitro. [J Cell Biochem] Abstract

Skin Cell Heterogeneity in Development, Wound Healing, and Cancer

The authors discuss recent insights into how these distinct cell populations are maintained and coordinated during development, homeostasis, and wound healing. They highlight the importance of the local environment, or niche, in cellular plasticity. They also discuss new mechanisms that have been identified as influencing wound repair and cancer progression. [Trends Cell Biol] Full Article

Overview of Silk Fibroin Use in Wound Dressings

Natural polymeric-based dressings are of central interest due to their outstanding biocompatibility, biodegradability, low toxicity, and non-allergenic nature. Among them, silk fibroin (SF) has exceptional characteristics as a wound dressing. The authors describe recent advances in the development of SF-based wound dressings for skin regeneration [Trends Biotechnol] Abstract

Visit our reviews page to see a complete list of reviews in the dermal cell research field.

NewLink Genetics Announces Final Results from Phase II Studies of Indoximod in Advanced Melanoma and Metastatic Pancreatic Cancer

NewLink Genetics Corporation announced that abstracts from two Phase II studies of indoximod, used in combination with other agents, are now available. Additional data will be presented. [Press release from NewLink Genetics Corporation discussing research to be presented at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago] Press Release

Celularity and New York Medical College Partner on a Breakthrough Study to Treat RDEB with Human Placental Derived Stem Cells

Celularity, Inc., announced that it is sponsoring an investigative study on the use of its proprietary human placental derived stem cells to treat recessive dystrophic epidermolysis bullosa. [Celularity (PR Newswire Association LLC.)] Press Release

U.S. FDA Grants Fast Track Designation for Krystal Biotech’s KB103 for the Treatment of Dystrophic Epidermolysis Bullosa

Krystal Biotech Inc. announced that the FDA has granted Fast Track designation to KB103 for the treatment of dystrophic epidermolysis bullosa. [Krystal Biotech Inc.] Press Release

BERG Announces FDA Orphan-Drug Designation of BPM 31510 for the Treatment of Patients with Epidermolysis Bullosa

BERG, LLC announced that the FDA has granted orphan-drug designation for the company’s lead product candidate, BPM 31510, for the treatment of patients with epidermolysis bullosa. [BERG, LLC (PR Newswire Association LLC)] Press Release

Synedgen Receives FDA 510(k) Clearance for Catasyn^™ Advanced Technology Wound Hydrogel

Synedgen announced that it has received 510(k) clearance from the FDA to market its Catasyn^™ Advanced Technology Wound Hydrogel both under the direction of a health care professional and over-the-counter. [Synedgen] Press Release

Dupixent^® (Dupilumab) Showed Positive Phase III Results in Adolescents with Inadequately Controlled Moderate-to-Severe Atopic Dermatitis

A pivotal Phase III trial evaluating Dupixent^® to treat moderate-to-severe atopic dermatitis in adolescents met its primary and key secondary endpoints. [Sanofi-Aventis U.S. LLC] Press Release

Realm Therapeutics Completes Enrollment in Phase II Study of PR022 for Atopic Dermatitis

Realm Therapeutics plc announced that the company has completed enrollment in its Phase II study of PR022, Realm’s first-in-class topical IL-4 / IL-13 inhibitor, for the treatment of atopic dermatitis. [Realm Therapeutics plc] Press Release

XBiotech Announces First Patient in Phase II Study Evaluating MABp1 in Patients with Atopic Dermatitis

XBiotech Inc. announced that the first patient has been enrolled in its Phase II open label, dose escalation clinical study evaluating MABp1 in patients with moderate to severe atopic dermatitis. [XBiotech Inc.] Press Release

Italy’s New Prime Minister Defended Discredited Stem Cell Therapy

The electoral victory of two populist parties in March had Italian scientists worried that a new era of antiscientific policies might be around the corner—and yesterday’s appointment of Giuseppe Conte as the country’s new prime minister is making some even more nervous. [ScienceInsider] Editorial

Swedish Court Blocks New Home for Nobel Foundation

A Swedish court has blocked construction of a controversial new Nobel Center planned for central Stockholm’s waterfront. The eight-story, brass-clad structure is expected to serve as a hub for the Nobel Foundation’s activities, including the annual December award ceremonies for the world’s most prestigious science prizes. [ScienceInsider] Editorial

Scientist Who Received Millions from NIH Leaves Alabama Posts

A professor who received about $5 million in grants from the National Institutes of Health left his posts at the University of Alabama, Birmingham (UAB), and Birmingham VA Medical Center last year after an investigation found evidence of image manipulation in 20 of his papers, Retraction Watch has learned. [The Scientist] Editorial

NEW The New York Stem Cell Foundation (NYSCF) Conference
October 23-24, 2018
New York, New York, United States

Visit our events page to see a complete list of events in the community.

NEW Assistant, Associate or Full Professor – Regenerative Medicine (University of San Diego)

Postdoctoral Fellow – Skin Stem Cells & Wound Healing (Johns Hopkins University)

Postdoctoral Fellow – Cancer Signaling & Trascription (The Francis Crick Institute)

Associate Professor or Professor – Skin Cancer (The University of Texas M.D. Anderson Cancer Center)

Postdoctoral Fellow – Psoriasis Research (Case Western Reserve University)

Postdoctoral Fellow – Skin Cancer Biology (UT Southwestern Medical Center)

Postdoctoral/Research Scientist – Cancer Metabolism (Wake Forest Comprehensive Cancer Center)

Postdoctoral Researcher – Melanoma (Ghent University)

Faculty Position – Developmental Biology and Regenerative Medicine (Seattle Children’s Research Institute)

PhD or Postdoctoral Position – Tissue Repair, Stem Cell Fate and Tumor Heterogeneity (Université Libre de Bruxelles)

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