China
Africa
Explore chapters and articles related to this topic
Overproduction of Hyaluronan in the Tumor Stroma
Published in Róza Ádány, Tumor Matrix Biology, 2017
Warren Knudson, Cheryl B. Knudson
The expression of CD44 in high-grade gliomas is elevated in comparison to normal brain tissue.163 This finding introduces a new perspective on results presented earlier by Gately and co-workers.164 They reported that, although there are glioma-specific antigens, patients make insignificant cellular immune responses to their tumors, suggesting that gliomas have some properties allowing them to escape cellular immune attack. Human glioma cell lines were studied in lysis assays with cytolytic lymphocytes. When glioma cells were cultured with peripheral blood mononuclear cells, the glioma cells assembled hyaluronan-enriched pericellular matrices. At the same time, lysis of the glioma cells by cytolytic lymphocytes decreased.164 Whiteside and Buckingham100 have detected a soluble factor produced by peripheral blood mononuclear cells that stimulates normal fibroblasts to increase their synthesis of hyaluronan and chondroitin sulfate proteoglycan. Gately et al. also reported that the glioma cells responded to a peripheral blood mononuclear cell conditioned media factor by assembling hyaluronan-dependent pericellular matrices.164 These pericellular matrices could be removed by hyaluronidase treatment, thus abrogating the immune protective effect and restoring the lymphocyte cytolysis. These hyaluronan-dependent pericellular matrices are likely anchored by CD44 receptors. The matrix itself, like those formed on carcinoma cells in our laboratories with exogenous components, likely contains hyaluronan together with a matrix hyaladherin such as neurocan, hyaluronectin, or glial hyaluronan-binding protein (related to versican).
The extracellular matrix of the blood–brain barrier: structural and functional roles in health, aging, and Alzheimer’s disease
Published in Tissue Barriers, 2019
May J. Reed, Mamatha Damodarasamy, William A. Banks
The lecticans are specific brain CSPGs characterized by structural similarities: a central core protein that binds CS GAG side chains; an N-terminal globular G1 domain with a link domain that binds HA, and a C-terminal G3 domain with a lectin-type sequence. The lecticans include: the large aggrecan that contains an additional G2 domain, three forms of versican (V0, V1, and V2), neurocan, and brevican.59 Individual lectican molecules differ in the number of CS-GAG chains attached to their core proteins, with over one hundred GAG side chains being found in aggrecan, which can be over 400 kDa, and as little as zero to five GAG chains being found in brevican and neurocan. Lecticans are produced by several cell types in the CNS, including neurons and astrocytes, and are well studied for their contribution to perineural nets (PNNs) in the brain parenchyma. It is worth noting that brevican, aggrecan, neurocan and versican differ in their relevance to the glycocalyx in the adult brain. Neurocan is present primarily during development, brevican has low levels of expression in adult brain and aggrecan is dominant in the PNNs, leaving versican as the primary CSPG in the adult brain vasculature and glycocalyx.59,60
Neuroinflammation and Optic Nerve Regeneration: Where Do We Stand in Elucidating Underlying Cellular and Molecular Players?
Published in Current Eye Research, 2020
Lien Andries, Lies De Groef, Lieve Moons
Over the past decades, several factors underlying the limited axonal regeneration capacity in the adult mammalian CNS have been identified. First of all, there is a strong extrinsic inhibitory environment in the injured CNS due to the myelin debris left behind after axonal degeneration and the production of myelin-derived inhibitory factors (e.g. neurite growth inhibitor (Nogo A), oligodendrocyte-myelin glycoprotein (OMgp) and myelin-associated glycoprotein (MAG)).3,14,15 Myelin debris is also an inflammatory modulator affecting the inflammatory response by directly influencing the phagocytosing macrophages and microglia. In most cases, it is pro-inflammatory, but the effect depends on the cellular and environmental conditions under which the debris is phagocytosed.16 Indeed, secondly, a prominent reactivation of astrocytes and microglia and the influx of blood-borne inflammatory cells at the site of CNS damage, induce a neuroinflammatory response resulting in the formation of a glial scar, which represents an important barrier for axonal regrowth. The activated myeloid and glial cells express various cytokines and growth factors triggering the release of inhibitory molecules at the glial scar, such as Semaphorin 3A, Slit-1, Tenascin-R, chondroitin sulphate proteoglycans (CSPGs), neurocan, versican, and neuron-glia antigen 2 (NG2)).14,17–24 A third process limiting axonal regeneration occurs in the retina, where neurotrophic factors, e.g. brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), glial-derived neurotrophic factor (GDNF), known to be important to support axonal regeneration, seem insufficiently expressed in the adult CNS.25–29 Finally, mature neurons have a low intrinsic growth potential due to a reduced expression of growth factors like growth-associated protein 43 (GAP-43), and small intracellular signaling molecules, e.g. cyclic adenosine monophosphate (cAMP)).15,30