Extracellular Matrix News Volume 11.18 | May 14 2020

TOP STORY

Minimal Lactazole Scaffold for In Vitro Thiopeptide Bioengineering

Systematic dissection of lactazole biosynthesis revealed remarkable substrate tolerance of the biosynthetic enzymes and led to the development of the minimal lactazole scaffold, a construct requiring only six post-translational modifications for macrocyclization. [Nat Commun] Full Article

(Ranked by impact factor of the journal)

Collagen Microarchitecture Mechanically Controls Myofibroblast Differentiation

Researchers combined experimental and computational approaches to investigate the hypothesis that the microarchitecture of fibrillar collagen networks mechanically regulated myofibroblast differentiation of adipose stromal cells independent of bulk stiffness. [Proc Natl Acad Sci USA] Abstract

Metformin, AMPK Activator Inhibits Activation of Fibroblast-Like Synoviocytes but Promotes Hyaluronan and Proteoglycan Link Protein 1 Secretion

AMPK levels positively correlated with many inflammatory indexes in rheumatoid arthritis (RA) patients, especially in the affected synovium. In RA sera, a positive correlation between p-AMPK-α1 levels and DAS28 activity was found. [Mol Ther Methods Clin Dev] Abstract | Full Article | Graphical Abstract

Bimodal Magnetic Resonance and Optical Imaging of Extracellular Matrix Remodelling by Orthotopic Ovarian Tumors

Investigators applied the magentism transfer-magnetic resonance imaging protocol for longitudinal imaging of the stroma in orthotopic human ovarian cancer ES-2 xenograft model in CD1 athymic nude mice, and for orthotopically implanted ovarian PDX using a MR-compatible imaging window chamber implanted into NSG mice. [Br J Cancer] Full Article

Breast Fibroblasts and ECM Components Modulate Breast Cancer Cell Migration through the Secretion of MMPs in a 3D Microfluidic Co-Culture Model

A microfluidic model was used to study the effect of 3D heterogeneous ECMs on the migration distance of a highly invasive human breast cancer cell line, MDA-MB-231. Specifically, scientists showed that in the presence of normal breast fibroblasts, a fibronectin-rich matrix induced more cancer cell migration. [Cancers] Abstract | Full Article

Perlecan Knockdown Significantly Alters Extracellular Matrix Composition and Organization during Cartilage Development

To identify how perlecan knockdown affected the material properties of developing cartilage, the authors used imaging and liquid chromatography-tandem mass spectrometry to study the ECM in a murine model of Schwartz-Jampel syndrome, Hspg2C1532Y-Neo. [Mol Cell Proteomics] Abstract

Generation of Cell-Derived Matrices That Support Human NK Cell Migration and Differentiation

Researchers describe the generation of cell-derived matrices (CDMs) from a commonly used murine fetal liver stromal cell line. These CDMs were derived directly from the same EL08.1D2 stromal cell line known to support NK cell differentiation and contain ECM structural components fibronectin and collagen. [J Leukoc Biol] Abstract

Eyes Shut Homolog (EYS) Interacts with Matriglycan of O-Mannosyl Glycans Whose Deficiency Results in EYS Mislocalization and Degeneration of Photoreceptors

Since some laminin globular domain-containing proteins function by binding to the matriglycan moiety of O-mannosyl glycans, the authors hypothesized that EYS interacted with matriglycans as well. To test this hypothesis, they performed EYS Far-Western blotting assay and generated pomgnt1 mutant zebrafish. [Sci Rep] Full Article

Prostaglandin F2α Agonist-Induced Suppression of 3T3-L1 Cell Adipogenesis Affects Spatial Formation of Extracellular Matrix

Upon adipogenesis of the 3T3-L1 organoid, the effects of either Bimatoprost acid, or PGF2α were examined. During the adipogenesis, organoid size, lipid staining by BODIPY and expression of the ECM by immunocytochemistry and/or quantitative PCR were employed. [Sci Rep] Full Article

The Correlations between Structure, Rheology, and Cell Growth in Peptide-Based Multicomponent Hydrogels

Factorial analysis of the interactions between three hydrogel-forming peptides based on three different biological motifs, namely, fibronectin: Fmoc-GFFRGD, collagen: Fmoc-GFFGER, and laminin: Fmoc-DDIKVAV, was conducted through rheology and live cell imaging using L929 fibroblasts. [Polymer J] Abstract

Effect of Endostatin on Wnt Pathway of Stem-Like Cells in Bladder Cancer in Tumor Microenvironment

Scientists investigated the effect of endostatin on Wnt signaling pathway of stem-like cells in bladder cancer in tumor microenvironment. The qRT-PCR assay and western blot were conducted to evaluate related factors expressions of Wnt signaling pathway in both bladder cancer 5637 cells and stem cells. [Mol Biol Rep] Abstract

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Pancreatic Cancer Stroma: An Update on Therapeutic Targeting Strategies

The three dominant entities in the pancreatic ductal adenocarcinoma (PDAC) stroma are ECM, vasculature and cancer-associated fibroblasts. The ECM can function as a barrier to effective drug delivery to PDAC cancer cells, and a multitude of strategies to target the ECM have been attempted in the past decade. [Nat Rev Gastroenterol Hepatol] Abstract

Restoring Synovial Homeostasis in Rheumatoid Arthritis by Targeting Fibroblast-Like Synoviocytes

The authors provide an overview of advances in understanding of fibroblast-like synoviocytes biology and highlights omics approaches and studies that hold promise for identifying future therapeutic targets. [Nat Rev Rheumatol] Abstract

Decellularized Extracellular Matrix for Bioengineering Physiomimetic 3D In Vitro Tumor Models

Investigators review current and upcoming methodologies for chemical modification of decellularized (d)ECM-based biomaterials and advanced bioprocessing into organotypic 3D solid tumor models. A comprehensive review of disruptive advances and shortcomings of exploring dECM-based biomaterials for recapitulating the native tumor-supporting matrix is also provided. [Trends Biotechnol] Abstract

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

ASCO: Novartis’ Tafinlar-Mekinist Combo Gets a Boost from PD-1 Immunotherapy

Novartis’ cancer-fighting duo Tafinlar and Mekinist alongside its experimental PD-1-blocking spartalizumab banished tumors in 44% of patients with advanced melanoma, early data from a Phase III study show. [Novartis (FierceBiotech)] Press Release

Amid the COVID-19 Pandemic, Some Scientists Bring the Bench Home

While some scientists have turned to writing manuscripts and grants and making inventories of their freezers to keep busy while away from the bench, others have brought experiments home, turning bathrooms, laundry rooms, and kitchens into makeshift labs-sometimes seeing an opportunity to explore new questions, other times trying out of desperation to prevent projects from moving backwards. [The Scientist] Editorial

Scientists Are Drowning in COVID-19 Papers. Can New Tools Keep Them Afloat?

Backed by large technology firms and the White House, a loose-knit army of data scientists, software developers, and journal publishers are racing to create digital collections holding thousands of freely available papers that could be useful to ending the pandemic, and scrambling to build data-mining and search tools that can help researchers quickly find the information they seek.” [ScienceInsider] Editorial

House Democrats Include Research Dollars in Latest Pandemic Relief Package

For US scientists, the good news is that the $3 trillion spending bill unveiled contains billions of dollars in new research funding. The bad news is that the bill is only a marker for negotiations with Senate Republicans and the White House on what more the federal government should do to help the country deal with the devastating economic and health effects of the pandemic. [ScienceInsider] Editorial

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NEW Postdoctoral Researcher – ECM in Cancer Progression (Biotech Research and Innovation Centre)

Quality Control – Regenerative Medicine (Centre for Commercialization of Regenerative Medicine)

Assistant Professor – Mammalian Synthetic Biology (Eindhoven University of Technology)

Posdoctoral Researcher – Stem Cells and Regenerative Medicine (Cedars-Sinai Regenerative Medicine Institute)

PhD Studentship – 3D Bioprinting of Tissues (Uppsala University)

Postdoctoral Researcher – Regenerative Medicine (ShanghaiTech University)

Principle Investigator – Regenerative Medicine (Guangzhou Institutes of Biomedicine and Health)

Faculty Member – Lung ECM Biology (NIH National Institute of Environmental Health Sciences)

Researcher – Biomaterials Scientist (Aspect Biosystems)

Research Associate – Oncology (Zymeworks, Inc.)

Research Scientist – Tumor Microenvironment (Systimmune, Inc.)

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