Extracellular Matrix News Volume 11.06 | Feb 20 2020

TOP STORY

Reprogramming Normal Cells into Tumor Precursors Requires ECM Stiffness and Oncogene-Mediated Changes of Cell Mechanical Properties

Microenvironments approximating the normal softness of healthy tissues, or blunting cellular mechanotransduction, prevented oncogene-mediated cell reprogramming and tumor emergence. Receptor tyrosine kinase–Ras oncogenes empowered a disproportional cellular response to the mechanical properties of the cell’s environment, such that when cells experienced even subtle supra-physiological ECM rigidity they were converted into tumor-initiating cells. [Nat Mater] Abstract

(Ranked by impact factor of the journal)

Matrix Mechanics and Water Permeation Regulate Extracellular Vesicle Transport

Using engineered hydrogels, investigators demonstrated that the mechanical properties of the matrix regulated anomalous extracellular vescile (EV) transport under confinement. Matrix stress relaxation allowed EVs to overcome the confinement, and a higher crosslinking density facilitated a fluctuating transport motion through a polymer mesh, which led to free diffusion and fast transport. [Nat Nanotechnol] Abstract

Oncogenic Kras Driven Metabolic Reprogramming in Pancreas Cancer Cells Utilizes Cytokines from the Tumor Microenvironment

Researchers showed that Kras drove cell autonomous expression of type I cytokine receptor complexes in cancer cells that in turn were capable of receiving cytokine growth signals provided by invading TH2 cells in the microenvironment. Early neoplastic lesions showed close proximity of Kras cancer cells and TH2 cells producing IL4 and IL13. [Cancer Discov] Abstract

Dynamic Buffering of Extracellular Chemokine by a Dedicated Scavenger Pathway Enables Robust Adaptation during Directed Tissue Migration

The authors showed that tissues exposed to acute “chemokine floods” halted transiently before they perfectly adapted, i.e., returned to the baseline migration behavior in the continued presence of elevated chemokine levels. A chemokine-triggered phosphorylation of the atypical chemokine receptor Cxcr7b re-routed it from constitutive ubiquitination-regulated degradation to plasma membrane recycling, thus coupling scavenging capacity to extracellular chemokine levels. [Dev Cell] Full Article | Graphical Abstract

Microcystin-LR Ameliorates Pulmonary Fibrosis via Modulating CD206⁺ M2-Like Macrophage Polarization

Scientists demonstrated that chronic exposure of microcystin-leucine arginine (LR) by oral administration for weeks attenuated the pulmonary fibrosis both oin bleomycin-induced rat and fluorescein isothiocyanate-induced mouse models. Data further indicated that treatment with microcystin-LR substantially reduced TGF-β1/Smad signaling in rat pulmonary tissues. [Cell Death Dis] Full Article

Conserved Role of Matrix Metalloproteases 2 and 9 in Promoting the Migration of Neural Crest Cells in Avian and Mammalian Embryos

Researchers explored the role of the gelatinases in executing neural crest cell migration, by determining whether matrix metalloproteases (MMP)2 and/or MMP9 regulated migration across species in singular, combined, or redundant manners. Chick and mouse embryos were utilized to compare expression and activity of both MMPs using genetic and pharmacological approaches in multiple in vivo and ex vivo assays. [FASEB J] Full Article

Platelet-Derived Transforming Growth Factor-β1 Promotes Keratinocyte Proliferation in Cutaneous Wound Healing

The authors investigated the specific role of platelet-derived TGFβ1 in cutaneous wound healing. Using a transgenic mouse with a targeted deletion of TGFβ1 in megakaryocytes and platelets, they showed for the first-time that platelet-derived TGFβ1 contributed to epidermal and dermal thickening and cellular turnover after excisional skin wounding. [J Tissue Eng Regen Med] Abstract

M₃ Receptor Modulates Extracellular Matrix Synthesis via ERK1/2 Signaling Pathway in Human Bladder Smooth Muscle Cells

Researchers investigated the effect of muscarinic receptors on the synthesis of ECM in human bladder smooth muscle cells (HBSMCs) and the involvement of intracellular signal transducers. The results indicated that M₁-M₅ muscarinic receptors were all encoded in HBSMCs. [J Cell Biochem] Abstract

Deficiency of αII-Spectrin Affects Endothelial Cell-Matrix Contact and Migration Leading to Impairment of Angiogenesis In Vitro

After siRNA- and shRNA-mediated knockdown of αII-spectrin, investigators assessed its expression and that of its partners and adhesion proteins using western blotting. The phenotypes of the control and spectrin-depleted cells were examined using immunofluorescence and video microscopy. [Cell Mol Biol Lett] Full Article

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Regulation of Oligodendrocyte Functions: Targeting Lipid Metabolism and Extracellular Matrix for Myelin Repair

The authors describe how altered lipid metabolism in oligodendrocytes influences the pathogenesis of demyelination, and they show that several FDA-approved drugs with a previously unknown remyelination potential do act on cholesterol and lipid biosynthetic pathways. [J Clin Med] Abstract | Download Full Article

Effect of the Nano/Microscale Structure of Biomaterial Scaffolds on Bone Regeneration

Scaffold-based tissue engineering is a promising strategy for bone regenerative medicine, because biomaterial scaffolds show advanced mechanical properties and a good degradation profile, as well as the feasibility of controlled release of growth and differentiation factors or immobilizing them on the material surface. [Int J Oral Sci] Full Article

The Extracellular Matrix: An Accomplice in Gastric Cancer Development and Progression

Investigators provide a comprehensive overview regarding expression patterns of ECM components and cognate receptors described in normal gastric epithelium, pre-malignant lesions, and gastric carcinomas. Important insights are also discussed for the use of ECM-associated molecules as predictive bio-markers of the disease or as potential targets in gastric cancer. [Cells] Abstract | Download Full Article

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Baylor Researchers Receive Nearly $2.7 Million in CPRIT Grants

Baylor College of Medicine has been awarded nearly $2.7 million by the Cancer Prevention and Research Institute of Texas (CPRIT) to support new cancer research. 55 new grants totaling more than $78 million were awarded to institutions across Texas, including three individual investigator grants to Baylor College of Medicine, to advance the fight against cancer. [Baylor College of Medicine] Press Release

ATS Foundation Research Program/Pulmonary Hypertension Association Names 2019 Partner Grant Awardees

The ATS Foundation Research Program/Pulmonary Hypertension Association has awarded Rahul Kumar, PhD, of the University of California, San Francisco, a $80,000 Foundation Partner grant. A $50,000 Foundation Partner grant was awarded to Jason Boehme, MD, also of the University of California, San Francisco. Ke Yuan, PhD, of Boston Children’s Hospital is the 2019 recipient of the Aldrighetti Research Award for Young Investigators. [The ATS Foundation (Newswise, Inc.)] Press Release

The Next Chapter for African Genomics

Nigeria is poised to become a hub for genetics research, but a few stubborn challenges block the way. [Nature News] Editorial

Scholars Debate Causes of Women’s Underrepresentation in STEM

Two new commentaries on a contested 2018 study about gender disparities in STEM fields clash over whether sex differences or social inequalities are to blame for the lack of women scientists and engineers. [The Scientist] Editorial

NEW Diverse Organisms and Common Mechanisms in Cell-Cell Fusion
May 31-June 5, 2020
Easton, Massachusetts, United States

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NEW Investigator – Single Cell Genomics (GlaxoSmithKline USA)

NEW Researcher – Biomaterials Scientist (Aspect Biosystems)

Postdoctoral Researchers – Regulatory RNA and Cell-Cell Communication (Brigham and Women’s Hospital)

Postdoctoral Fellow – Mechanisms of TGF-Beta Activiation (Genentech, Inc.)

Postdoctoral Fellow – Extracellular Superoxide Dismutase (Vascular Biology Center)

Postdoctoral Researcher – Computational Biology (Medical University of Gdańsk)

Research Associate – Oncology (Zymeworks, Inc.)

Research Scientist – Tumor Microenvironment (Systimmune, Inc.)

Scientist – Regenerative Medicine (Xtant Medical, Inc.)

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

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