Extracellular Matrix News Volume 11.02 | Jan 23 2020

TOP STORY

Remodeling of Metastatic Vasculature Reduces Lung Colonization and Sensitizes Overt Metastases to Immunotherapy

Investigators showed in primary mouse lung cancer that normalization of tumor vasculature by LIGHT and a vascular targeting peptide (VTP) prevents cancer cell intravasation. Further, LIGHT-VTP efficiently targeted pathological blood vessels in the pre-metastatic niche, reducing vascular hyper-permeability and ECM deposition, thus blocking metastatic lung colonization. [Cell Rep] Full Article | Graphical Abstract

(Ranked by impact factor of the journal)

Parallel Lineage-Tracing Studies Establish Fibroblasts as the Prevailing In Vivo Adipocyte Progenitor

Using Cre recombinases labeling distinct vascular lineages, researchers conducted parallel lineage tracing experiments to assess their degree of contribution to de novo adipogenesis. Although they detected occasional adipocytes that were lineage traced by endothelial or mural recombinases, these were rare events. [Cell Rep] Full Article | Graphical Abstract

Relaxation of Extracellular Matrix Forces Directs Crypt Formation and Architecture in Intestinal Organoids

Allyl sulfide hydrogels were employed as a synthetic ECM mimic, but with photocleavable bonds that temporally regulated the material’s bulk modulus. By varying the extent of matrix softening, it was demonstrated that crypt formation, size, and number per colony were functions of matrix softening. [Adv Healthc Mater] Abstract

Senescent Mesenchymal Stem Cells Remodel Extracellular Matrix Driving Breast Cancer Cells to a More-Invasive Phenotype

Scientists investigated senescence-associated biophysical changes in mesenchymal stem cells (MSCs) and how this influences cancer cell behavior in a 3D matrix interface model. Although senescent MSCs were far less motile than pre-senescent MSCs, they induced an invasive breast cancer phenotype, characterized by increased spheroid growth and cell invasion in collagen gels. [J Cell Sci] Abstract

miR-873-3p Targets HDAC4 to Stimulate Matrix Metalloproteinase-13 Expression Upon Parathyroid Hormone Exposure in Rat Osteoblasts

Investigators hypothesized that PTH upregulates the miRNAs targeting HDAC4, which could lead to increased Runx2 activity and matrix metalloproteinase-13 expression in rat osteoblastic cells. They identified several miRNAs that putatively targeted rat HDAC4 using bioinformatics tools. miR-873-3p was significantly upregulated by PTH in rat osteoblasts. [J Cell Physiol] Abstract

miR-130a and Tgfβ Content in Extracellular Vesicles Derived from the Serum of Subjects at High Cardiovascular Risk Predicts Their In Vivo Angiogenic Potential

To identify patients that may benefit from autologous serum-derived extracellular vesicles (sEV) administration for pro-angiogenic purposes, sEV angiogenic capability as evaluated in type 2 diabetic (T2DM) subjects, in obese individuals with and without T2DM, and in subjects with ischemic disease. [Sci Rep] Full Article

Extracellular NAD⁺ Enhances PARP-Dependent DNA Repair Capacity Independently of CD73 Activity

Researchers investigated whether expression of CD73 impacted intracellular nicotinamide adenine dinucleotide (NAD)⁺ content and NAD⁺-dependent DNA repair capacity. Reduced intracellular NAD⁺ levels suppressed recruitment of the DNA repair protein XRCC1 to sites of genomic DNA damage and impacted the amount of accumulated DNA damage. [Sci Rep] Full Article

CD248 and Integrin Alpha-8 Are Candidate Markers for Differentiating Lung Fibroblast Subtypes

Researchers characterized distinct mouse lung fibroblast subpopulations isolated by fluorescence-activated cell sorting and performed microarray analysis to identify molecular markers that could be useful for human lung fibroblast classification. Based on the expression of these markers, they evaluated the fibroblast-like cell subtype localization in normal human lung samples and lung samples from patients with idiopathic pulmonary fibrosis. [BMC Pulm Med] Full Article

Dopamine Receptor Activation Modulates the Integrity of the Perisynaptic Extracellular Matrix at Excitatory Synapses

The authors report that neuromodulation via D1-type dopamine receptors could induce targeted ECM proteolysis specifically at excitatory synapses of rat cortical neurons via proteases ADAMTS-4 and -5. They showed that receptor activation induces increased proteolysis of brevican and aggrecan, two major constituents of the adult ECM both in vivo and in vitro. [Cells] Abstract | Download Full Article

Principles of Cell Circuits for Tissue Repair and Fibrosis

Investigators established a cell-circuit framework for the myofibroblast-macrophage circuit in wound healing, including the accumulation of scar-forming ECM. They found that fibrosis results from multistability between three outcomes, which they termed ‘hot fibrosis’ characterized by many macrophages, ‘cold fibrosis’ lacking macrophages, and normal wound healing. [iScience] Abstract | Graphical Abstract

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The Importance of Exosomal PDL1 in Tumor Immune Evasion

Programmed cell death 1 ligand 1 (PDL1) can be expressed on the surface of tumor cells, immune cells and other cells in the tumor microenvironment but is also found in extracellular forms. Recent studies have explored the importance of different forms of extracellular PDL1, such as on exosomes or as a freely soluble protein, and have shown that PDL1-expressing exosomes can inhibit anti-tumor immune responses. [Nat Rev Immunol] Abstract

Communication, Cross Talk, and Signal Integration in the Adult Hippocampal Neurogenic Niche

Adult hippocampal neurogenesis is sensitive to experiences, suggesting that it may represent an adaptive mechanism by which hippocampal circuitry is modified in response to environmental demands. Experiential information is conveyed to radial glia-like neural stem cells, progenitors, and adult-born dentate granule cells via the neurogenic niche that is composed of diverse cell types, extracellular matrix, and afferents. [Neuron] Full Article

miRNAs as Influencers of Cell-Cell Communication in Tumor Microenvironment

Investigators discuss the role of miRNAs in the pathogenesis of multicomplex diseases, such as Alzheimer’s disease, obesity, and cancer, focusing on the contribution of both intracellular miRNAs, and of released extracellular miRNAs in the establishment and development of cancer niche. They also review growing evidence suggesting the use of miRNAs as novel targets or potential tools for therapeutic applications. [Cells] Full Article

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

Abeona Therapeutics Initiates Pivotal Phase III Clinical Trial Evaluating EB-101 Gene Therapy for Recessive Dystrophic Epidermolysis Bullosa

Abeona Therapeutics Inc. announced that it has received Institutional Review Board approval from Stanford University to commence the VIITAL™ study, the company’s pivotal Phase III clinical trial evaluating EB-101 for the treatment of recessive dystrophic epidermolysis bullosa. [Abeona Therapeutics Inc.] Press Release

Chi-Med Initiates a Phase II Trial of Surufatinib in Combination with Tuoyi in Patients with Advanced Solid Tumors

Hutchison China MediTech Limited has initiated a Phase II study in China of surufatinib in combination with Tuoy in patients with advanced solid tumors. This follows the recent completion of the Phase I dose finding study and successful establishment of the Phase II combination dosing regimen for surufatinib and Tuoyi. [Hutchison China MediTech Limited] Press Release

Nine Researchers Receive EMBO Installation Grants to Establish Independent Laboratories

EMBO is pleased to announce that nine life scientists have been selected to receive Installation Grants, which will support them in establishing independent laboratories in the Czech Republic, Poland, Portugal and Turkey. [EMBO (EurekAlert!)] Press Release

NEW Keystone Symposia: Tumor Metabolism
March 8-12, 2020
Banff, Alberta, Canada

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NEW Postdoctoral Position – Blood Engineering and Cell Communication (Karolinska Institutet)

Research Associate – Bioengineering (STEMCELL Technologies Inc.)

Postdoctoral Researcher – Computational Biology (Medical University of Gdańsk)

Research Associate – Oncology (Zymeworks Inc.)

Research Fellow – Cell Signaling (University of Sussex)

Research Scientist – Tumor Microenvironment (Systimmune Inc.)

Postdoctoral Researcher – Tumor Microenvironment (Personalis, Inc.)

Postdoctoral Research Fellow – Tumor Microenvironment (Fred Hutchinson Cancer Research Center)

Postdoctoral Position – Inter- and Extracellular Protein Interactions (University of Southern California)

Scientist – Regenerative Medicine (Xtant Medical, Inc.)

Master Thesis – Hydrogels and Microfluid Environments (Karlsruhe Institute of Technology)

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