Modulation of Microenvironment Signals by Proteolytic Shedding of Cell Surface Extracellular Matrix Receptors.

Yoshifumi Itoh

doi:10.3389/fcell.2021.736735

Abstract

Multicellular organisms are composed of cells and extracellular matrix (ECM). ECM is a network of multidomain macromolecules that fills gaps between cells. It acts as a glue to connect cells, provides scaffolding for migrating cells, and pools cytokines and growth factors. ECM also directly sends signals to the cells through ECM receptors, providing survival signals and migration cues. Altogether, ECM provides a correct microenvironment for the cells to function in the tissue. Although ECM acts as a signaling molecule, they are insoluble solid molecules, unlike soluble receptor ligands such as cytokines and growth factors. Upon cell binding to the ECM through ECM receptors and signals transmitted, cells then need to have a mechanism to release from ECM to prevent prolonged signals, which may be tumorigenic, and migrate on ECM. One effective means to release the cells from ECM is to cleave the ECM receptors by proteinases. In this mini-review, current knowledge of ECM receptor shedding will be discussed.

Highlights

Multicellular organisms consist of cells and extracellular matrix (ECM)
membrane-type 1 matrix metalloproteinases (MMPs) (MT1-MMP) forms a complex with CD44 through the hemopexin domain (Mori et al, 2002), and ADAM10 was shown to form a complex with DDR1 (Shitomi et al, 2015)
The shedding event can be triggered by the interaction of the ECM receptor with the ligand ECM

Summary

Yoshifumi Itoh*

Edited by: Frederic Saltel, INSERM U1053 Bordeaux Recherche en Oncologie Translationnelle, France. It acts as a glue to connect cells, provides scaffolding for migrating cells, and pools cytokines and growth factors. ECM directly sends signals to the cells through ECM receptors, providing survival signals and migration cues. ECM acts as a signaling molecule, they are insoluble solid molecules, unlike soluble receptor ligands such as cytokines and growth factors. Upon cell binding to the ECM through ECM receptors and signals transmitted, cells need to have a mechanism to release from ECM to prevent prolonged signals, which may be tumorigenic, and migrate on ECM. One effective means to release the cells from ECM is to cleave the ECM receptors by proteinases. In this mini-review, current knowledge of ECM receptor shedding will be discussed

INTRODUCTION

Proteolytic Shedding of ECM Receptors

DISCOIDIN DOMAIN RECEPTORS

CONCLUDING REMARKS