Hyaluronan-dependent pericellular matrix☆

Abstract

Hyaluronan is a multifunctional glycosaminoglycan that forms the structural basis of the pericellular matrix. Hyaluronan is extruded directly through the plasma membrane by one of three hyaluronan synthases and anchored to the cell surface by the synthase or cell surface receptors such as CD44 or RHAMM. Aggregating proteoglycans and other hyaluronan-binding proteins, contribute to the material and biological properties of the matrix and regulate cell and tissue function. The pericellular matrix plays multiple complex roles in cell adhesion/de-adhesion, and cell shape changes associated with proliferation and locomotion. Time-lapse studies show that pericellular matrix formation facilitates cell detachment and mitotic cell rounding. Hyaluronan crosslinking occurs through various proteins, such as tenascin, TSG-6, inter-alpha-trypsin inhibitor, pentraxin and TSP-1. This creates higher order levels of structured hyaluronan that may regulate inflammation and other biological processes. Microvillous or filopodial membrane protrusions are created by active hyaluronan synthesis, and form the scaffold of hyaluronan coats in certain cells. The importance of the pericellular matrix in cellular mechanotransduction and the response to mechanical strain are also discussed.

A Role for Versican in the Development of Leiomyosarcoma

“…Data from the overexpression of HAS1-3 or perturbation of hyaluronan production in several cancer cell lines have suggested that the accumulation of hyaluronan stimulates growth, survival, invasion, and metastasis of cancer cells (66 -68). Thus, it is likely that both hyaluronan and versican participate in the formation of a permissive microenvironment around the LMS tumor cells to promote their proliferation (42,69). It is interesting to note that our data show that a maximal proliferative response is achieved when the two molecules are added together, suggesting that a versican-hyaluronan complex may be optimal for the proliferative response of the LMS cells.…”

“…42), we asked whether differences existed in the extent of pericellular coat formation between LMS tumor cells and LMS tumor cells in which versican and hyaluronan had been reduced by siRNA to versican. Using a particle exclusion assay, the presence of a distinct pericellular matrix around cultured cells was demonstrated by the exclusion of fixed red blood cells.…”

Two Novel Functions of Hyaluronidase-2 (Hyal2) Are Formation of the Glycocalyx and Control of CD44-ERM Interactions

“…Although we did not measure any difference in the hyaluronidase activity of cell extracts, including cell membrane fractions, from BB16 versus Hyal2-overexpressing clones, we cannot exclude the possibility that Hyal2 has a highly localized HA-degrading activity, reducing the mean size of HA molecules that are attached specifically to the cell surface. This type of attachment requires HA synthases, HA receptors, aggregating proteoglycans, and covalent HA-protein linkages (42,48,49). Hyal2 itself may be part of this macromolecular complex.…”

Acide hyaluronique et matrice extracellulaire : une molécule primitive ?

“…Cette matrice péricellulaire excède souvent 20µm ce qui correspond plus ou moins à la longueur d'un polymère d'acide hyaluronique maintenu sous une conformation complètement étirée par association avec des hyalectans, aggrécan dans le cas des chondrocytes et versican dans le cas des fibroblastes et cellules musculaires lisses. Les HAS peuvent également retenir les polymères d'acide hyaluronique en voie de synthèse à la surface cellulaire Cette matrice péricellulaire hautement dynamique joue de multiples rôles [10]. Elle a été impliquée dans l'assemblage des macromolécules de la matrice extracellulaire, collagène et fibronectine, dans le contrôle de la prolifération et le phénotype migratoire de certaines cellules activées par des facteurs de croissance, comme le PDGF sur les cellules musculaires lisses.…”