Extracellular Matrix News Volume 10.24 | Jun 27 2019

TOP STORY

Anchoring of Intratumorally Administered Cytokines to Collagen Safely Potentiates Systemic Cancer Immunotherapy

Scientists found that intratumoral administration of a cytokine fused to the collagen-binding protein lumican prolonged local retention and markedly reduced systemic exposure. Combining local administration of lumican-cytokine fusions with systemic immunotherapies improved efficacy without exacerbating toxicity in syngeneic tumor models and the Braf^V600E/Pten^fl/fl genetically engineered melanoma model. [Sci Transl Med] Abstract | Press Release

(Ranked by impact factor of the journal)

Switch-Like Enhancement of Epithelial-Mesenchymal Transition by YAP through Feedback Regulation of WT1 and Rho-Family GTPases

The integrity of expanding epithelial sheets depends on extracellular cues, including cell-cell and cell-matrix interactions. Researchers showed that the nano-scale topography of the ECM underlying epithelial cell layers could strongly affect the speed and morphology of the fronts of the expanding sheet, triggering partial and complete epithelial-mesenchymal transitions. [Nat Commun] Full Article | Press Release

Collagen XIII-Derived Ectodomain Regulates Bone Angiogenesis and Intracortical Remodeling

The authors studied bone homeostasis in collagen XIII (ColXIII)-overexpressing mice up to 72 weeks of age and observed a cortical bone overgrowth followed by a drastic bone loss, together with increased bone vascularization. They demonstrated that the ColXIII-derived ectodomain enhanced angiogenesis through β1-integrins and the JNK pathway. [Matrix Biol] Abstract

An Injectable, Click-Crosslinked, Cytomodulin-Modified Hyaluronic Acid Hydrogel for Cartilage Tissue Engineering

The click-crosslinked hyaluronic acid-cytomodulin hydrogel caused better chondrogenic differentiation of human periodontal ligament stem cells, as evidenced by Alcian blue and Safranin O staining, and greater increases in the expression of type II collagen, glycosaminoglycan content and SOX9, aggrecan, and type 2α1 collagen mRNA levels. [NPG Asia Mater] Full Article

3D Bioprinted Mammary Organoids and Tumoroids in Human Mammary Derived ECM Hydrogels

Investigators describe a methodology for generating mammary ECM extracts that could spontaneously gel to form hydrogels. These ECM hydrogels retained unique structural and signaling profiles that elicited differential responses when normal mammary and breast cancer cells were cultured within them. [Acta Biomater] Abstract | Graphical Abstract

Bi-Layered Micro-Fibre Reinforced Hydrogels for Articular Cartilage Regeneration

Production of sulphated glycosaminoglycans and collagen II was observed for the novel composite constructs cultured under mechanical conditioning without TGF-β1 supplementation and in static conditions with TGF-β1 supplementation, which confirmed the capability of the novel composite construct to support neo-cartilage formation upon mechanical stimulation. [Acta Biomater] Abstract | Graphical Abstract

Cigarette Smoke Induces Metabolic Reprogramming of the Tumor Stroma in Head and Neck Squamous Cell Carcinoma

Scientists examined the effects of cigarette smoke-exposed cancer-associated fibroblasts on metabolic coupling and tumor aggressiveness of head and neck squamous cell carcinoma (HNSCC). Cigarette smoke (CS) extract was generated by dissolving cigarette smoke in growth media. Fibroblasts were cultured in CS or control media. HNSCC cells were co-cultured in vitro and co-injected in vivo with CS- or control fibroblasts. [Mol Cancer Res] Abstract

Thy-1 Depletion and Integrin β3 Upregulation-Mediated PI3K-Akt-mTOR Pathway Activation Inhibits Lung Fibroblast Autophagy in Lipopolysaccharide-Induced Pulmonary Fibrosis

Challenge of the human lung fibroblast MRC-5 cell line with LPS resulted in significant upregulation of integrin β3, activation of the PI3K-Akt-mTOR pathway and inhibition of autophagy, which could be abolished by integrin β3 silencing by specific shRNA or treatment with the integrin β3 inhibitor cilengitide. [Lab Invest] Full Article

The Extracellular Matrix Proteoglycan Lumican Improves Survival and Counteracts Cardiac Dilatation and Failure in Mice Subjected to Pressure Overload

Cultured cardiac fibroblasts treated with lumican showed increased mRNAs for markers of myofibroblast differentiation, proliferation and expression of ECM molecules important for fibrosis, including collagens and collagen cross-linking enzyme lysyl oxidase. [Sci Rep] Full Article

Blockade of Thrombospondin-1 Ameliorates High Glucose-Induced Peritoneal Fibrosis through Downregulation of TGF-β1/Smad3 Signaling Pathway

Exposure of Met-5A cells to thrombospondin-1 increased TGF-β1 secretion, expression and bioactivity, triggered Smad3 phosphorylation, upregulated the expression of mesenchymal molecules including fibronectin, collagen type III, α-smooth muscle actin, Snail, and decreased calretinin expression. [J Cell Physiol] Abstract

Caffeic Acid Phenethyl Ester Inhibits UV-Induced MMP-1 Expression by Targeting Histone Acetyltransferases in Human Skin

Researchers investigated the inhibitory effect of caffeic acid phenethyl ester (CAPE) against ultraviolet (UV) irradiation-mediated matrix metalloproteinase (MMP)-1 expression and its underlying molecular mechanism. CAPE treatment suppressed UV-induced MMP-1 levels in both human dermal fibroblasts and human skin tissues. [Int J Mol Sci] Full Article

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Circular RNAs as Novel Regulators, Biomarkers and Potential Therapies in Fibrosis

The authors summarize current studies of circular RNAs in fibrosis and hopefully aid in better understanding the molecular mechanism of fibrosis and provide a basis to explore new therapeutic targets of fibrosis. [Epigenomics] Abstract

Visit our reviews page to see a complete list of reviews in the extracellular matrix research field.

SOFIE and University Clinic Heidelberg Sign License Agreement

SOFIE Inc. announced an exclusive global license with University Clinic Heidelberg for a class of molecular targeted diagnostics and radiotherapeutics that are designed to identify and break down cancer associated fibroblasts in tumor stroma and irradiate nearby cancer cells. [SOFIE Inc.] Press Release

Krystal Biotech Announces Positive Results from Phase II Clinical Trial (GEM-2 Study) of KB103 and Receives Regenerative Medicine Advanced Therapy (RMAT) Designation from FDA for KB103

Krystal Biotech, Inc. announced positive results from its Phase II placebo-controlled clinical trial of KB103 study and an update on results from Phase I study. KB103 is a replication-defective, non-integrating viral vector that has been engineered employing Krystal’s STAR-D platform to deliver functional human COL7A1 genes directly to the patients’ dividing and non-dividing skin cells. [Krystal Biotech, Inc.] Press Release

Acer Therapeutics Receives Complete Response Letter from US FDA for Use of EDSIVO™ (Celiprolol) in vEDS Patients

Acer Therapeutics Inc. announced it has received a Complete Response Letter from the FDA regarding its New Drug Application for EDSIVO™ for the treatment of vascular Ehlers-Danlos syndrome (vEDS). [Acer Therapeutics Inc. (GlobeNewswire, Inc.)] Press Release

NIH Probe of Foreign Ties Has Led to Undisclosed Firings—and Refunds from Institutions

An aggressive effort by the National Institutes of Health (NIH) to enforce rules requiring its grantees to report foreign ties is still gathering steam. But it has already had a major impact on the US biomedical research community. A senior NIH official tells ScienceInsider that universities have fired more scientists—and refunded more grant money—as a result of the effort than has been publicly known. [ScienceInsider] Editorial

Discrimination Drives LGBT+ Scientists to Think About Quitting

Nearly one-third of physical scientists from sexual and gender minorities in the United Kingdom have considered leaving their jobs because of their workplace climate, suggests a survey. And 18% who are lesbian, gay, bisexual, transgender or from other sexual and gender minorities (LGBT+) said they had experienced harassment, bullying or exclusionary behavior in the workplace. [Nature News] Editorial

NEW The Liver Meeting
November 8-12, 2019
Boston, Massachusetts, United States

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

NEW Postdoctoral Fellow – Role of Collagen in Tissue Repair & Regeneration (University of Pennsylvania)

Scientist – Matrix Biology (STEMCELL Technologies Inc.)

Research Lab Specialist – Tumor Microenvironment & Cell Behavior (University of Southern California)

Postdoctoral Postions – Tissue Engineering (University of Oslo)

Faculty Positions – Biochemistry & Molecular Biophysics (Washington University in St. Louis School of Medicine)

Postdoctoral Position – Bioengineering Cell Fate & Morphogeneis in Organoids (KU Leuven)

Postdoctoral Research Fellowships – Kidney Disease (Vanderbilt University Medical Center)

Postdoctoral Position – Experimental Systems Biology of Lung Regeneration & Fibrosis (Helmholtz Zentrum München)

Head of School – Biomedical Engineering (University of Sydney)

Postdoctoral Fellowship – Renal Extracellular Matrix Research (Vanderbilt University Medical Center)

Postdoctoral Scholar – Computational Modeling of Cell-Matrix Interactions (Washington University, St. Louis)

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