CD93 promotes β1 integrin activation and fibronectin fibrillogenesis during tumor angiogenesis

The Journal of Clinical Investigation
Roberta LuganoAnna Dimberg

Abstract

Tumor angiogenesis occurs through regulation of genes that orchestrate endothelial sprouting and vessel maturation, including deposition of a vessel-associated extracellular matrix. CD93 is a transmembrane receptor that is upregulated in tumor vessels in many cancers, including high-grade glioma. Here, we demonstrate that CD93 regulates β1 integrin signaling and organization of fibronectin fibrillogenesis during tumor vascularization. In endothelial cells and mouse retina, CD93 was found to be expressed in endothelial filopodia and to promote filopodia formation. The CD93 localization to endothelial filopodia was stabilized by interaction with multimerin-2 (MMRN2), which inhibited its proteolytic cleavage. The CD93-MMRN2 complex was required for activation of β1 integrin, phosphorylation of focal adhesion kinase (FAK), and fibronectin fibrillogenesis in endothelial cells. Consequently, tumor vessels in gliomas implanted orthotopically in CD93-deficient mice showed diminished activation of β1 integrin and lacked organization of fibronectin into fibrillar structures. These findings demonstrate a key role of CD93 in vascular maturation and organization of the extracellular matrix in tumors, identifying it as a potential target for...Continue Reading

References

Jan 1, 1996·The Journal of Cell Biology·K WennerbergR Fässler
Nov 27, 1999·The Journal of Biological Chemistry·S Tsukita, S Yonemura
Aug 19, 2000·Science·B St CroixK W Kinzler
Mar 9, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Peter J NorsworthyMarina Botto
Feb 3, 2005·Nature Reviews. Molecular Cell Biology·Satyajit K MitraDavid D Schlaepfer
Jul 9, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Suzanne S BohlsonAndrea J Tenner
Jul 10, 2007·Acta Neuropathologica·David N LouisPaul Kleihues
Nov 29, 2007·Journal of Translational Medicine·Vinay BhaskarVanitha Ramakrishnan
Aug 2, 2008·The New England Journal of Medicine·Patrick Y Wen, Santosh Kesari
Sep 23, 2008·Molecular and Cellular Neurosciences·Katrin FärberHelmut Kettenmann
Jan 2, 2009·Journal of Cell Science·David S Harburger, David A Calderwood
Jul 16, 2009·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Mallary C GreenleeSuzanne Slater Bohlson
Dec 2, 2009·BMC Cancer·Eleanor B Carson-WalterKevin A Walter
Aug 10, 2010·Annual Review of Cell and Developmental Biology·Purva SinghJean E Schwarzbauer
Sep 8, 2010·Current Opinion in Cell Biology·Hanna M Eilken, Ralf H Adams
Sep 28, 2010·Nature Cell Biology·Lars JakobssonHolger Gerhardt
Dec 9, 2010·Nature Biotechnology·Mathias UhlenFredrik Ponten
Jun 2, 2011·Nature Reviews. Drug Discovery·Peter Carmeliet, Rakesh K Jain
May 15, 2013·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Rakesh K Jain
Aug 28, 2013·Molecular & Cellular Proteomics : MCP·Sara ZanivanMatthias Mann
Mar 25, 2014·Nature Cell Biology·Katie BentleyHolger Gerhardt
Nov 18, 2014·Biochemical Society Transactions·Anna Dimberg
Mar 11, 2015·Nature Communications·Hiroyuki YamamotoRalf H Adams
Mar 5, 2016·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Peter J NoyRoy Bicknell
Jun 9, 2016·Vascular Pharmacology·Lena Claesson-Welsh
Jan 14, 2017·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Nancy WangTracy T Batchelor
Apr 25, 2017·Matrix Biology : Journal of the International Society for Matrix Biology·Eva AndreuzziMaurizio Mongiat
Sep 16, 2017·Matrix Biology : Journal of the International Society for Matrix Biology·Federico GalvagniMaurizio Orlandini
Feb 15, 2018·Nature·Michael VanlandewijckChrister Betsholtz

❮ Previous
Next ❯

Citations

Jul 10, 2019·The FEBS Journal·Kabir A KhanRoy Bicknell
Aug 23, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Haoche WeiHarry Mellor
Oct 4, 2019·Oncology Letters·Supriya BorahRajeeb K Swain
Jul 23, 2020·Investigative Ophthalmology & Visual Science·Gian Marco TosiMaurizio Orlandini
Dec 14, 2018·International Journal of Molecular Sciences·Eva AndreuzziMaurizio Mongiat
Apr 16, 2020·Proceedings of the National Academy of Sciences of the United States of America·Qingli LiangJianwei Jiao
Aug 28, 2020·Frontiers in Cell and Developmental Biology·Noriko M MatsumotoRei Ogawa
Jan 17, 2020·Scientific Reports·Hye Jung ParkJae-Hyun Lee
May 20, 2020·Frontiers in Cardiovascular Medicine·Menglan XiangEugene C Butcher
May 28, 2020·International Journal of Molecular Sciences·Eva AndreuzziMaurizio Mongiat
Nov 7, 2019·Cellular and Molecular Life Sciences : CMLS·Roberta LuganoAnna Dimberg
Oct 20, 2020·Experimental Eye Research·Kevin SchneiderM Cristina Kenney
Mar 25, 2021·Mathematical Biosciences and Engineering : MBE·Rui-Zhe ZhengXin-Yuan Li
Apr 24, 2021·Signal Transduction and Targeted Therapy·Jiacheng HuangYiting Qiao
May 3, 2021·The EMBO Journal·Magda N Hernández VásquezTaija Mäkinen
Jun 2, 2021·Matrix Biology : Journal of the International Society for Matrix Biology·Stefano BarberaMaurizio Orlandini
Aug 6, 2021·Molecular Cancer Research : MCR·Helen SheldonAdrian L Harris

❮ Previous
Next ❯

Datasets Mentioned

BETA
MBS2028221

Methods Mentioned

BETA
laser-capture microdissection
proximity ligation assay
confocal microscopy
transfection
coimmunoprecipitation
transfections
PCR
FACS

Software Mentioned

Duolink ImageTool
GraphPad
GraphPad Prism
IMARIS
MaxQuant
ImageJ

Related Concepts

Related Feeds

Angiogenesis Inhibitors to Treat Cancer

Cancer treatments including angiogenesis inhibitors prevent tumor cells from receiving nutrients and oxygen. Here is the latest research on angiogenesis inhibitors for the treatment of cancer.

Cell Signaling by Tyrosine Kinases

Receptor tyrosine kinases (RTKs) are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. RTKs have been shown not only to be key regulators of normal cellular processes but also to have a critical role in the development and progression of many types of cancer. Discover the latest research on cell signaling and RTK here.

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.