Matricellular protein tenascin C: Implications in glioma progression, gliomagenesis, and treatment

Abstract

Matricellular proteins are nonstructural extracellular matrix components that are expressed at low levels in normal adult tissues and are upregulated during development or under pathological conditions. Tenascin C (TNC), a matricellular protein, is a hexameric and multimodular glycoprotein with different molecular forms that is produced by alternative splicing and post-translational modifications. Malignant gliomas are the most common and aggressive primary brain cancer of the central nervous system. Despite continued advances in multimodal therapy, the prognosis of gliomas remains poor. The main reasons for such poor outcomes are the heterogeneity and adaptability caused by the tumor microenvironment and glioma stem cells. It has been shown that TNC is present in the glioma microenvironment and glioma stem cell niches, and that it promotes malignant properties, such as neovascularization, proliferation, invasiveness, and immunomodulation. TNC is abundantly expressed in neural stem cell niches and plays a role in neurogenesis. Notably, there is increasing evidence showing that neural stem cells in the subventricular zone may be the cells of origin of gliomas. Here, we review the evidence regarding the role of TNC in glioma progression, propose a potential association between TNC and gliomagenesis, and summarize its clinical applications. Collectively, TNC is an appealing focus for advancing our understanding of gliomas.

Extracellular Matrix Structure and Interaction with Immune Cells in Adult Astrocytic Tumors

“…Post-translation modification can give rise to proteins with different functions. Notably, the small fragment obtained by proteolytic processing displays functions that can be very different from those of the full-length protein (Fu et al 2022 ). In the embryo, TNC is widely expressed in the sites of morphogenesis around motile cells, and at different degrees in connective tissues, such as bone and cartilage, and in the central nervous system.…”

“…In the adult human organism, TNC is expressed only in connective tissues that bear tensile strength, below some epithelia and in stem cell niches, such as bone marrow, crypts of the intestine, bulge of hair follicles and bone marrow. In addition, TNC is also expressed in adult brain in both stem cells niches (astrocytes in the subventricular zone and granule cells in the hippocampus) and cerebellum (Fu et al 2022 ). TNC belongs to Tenascin family which includes Tenascin-W, Tenascin-X, and Tenascin-R.…”

“…These and other nonstructural proteins such as periostin ad SPARC are indicated as matricellular proteins which modulate cellular behavior by interacting with other structural and nonstructural ECM components: fibronectin, collagen, periostin, and fibrillin-2 as well as PGs of the lectican family and perlecan. In adult, TNC is re-expressed ectopically in a variety of pathologic situations, such as neuroinflammation, neurodegeneration, ischemia, and solid tumors including brain cancer (Di Vito et al 2021 ; Donato et al 1997 , 2009 ; Fu et al 2022 ). The highest level of TNC reported in glioma correlates with tumor grade.…”

“…The potentiality of TNC as therapeutic target has been previously evaluated. Many strategies aimed to silence or decrease TNC expression have been developed and detailed in (Fu et al 2022 ).…”

Evaluating nanoparticle localisation in glioblastoma multicellular tumour spheroids by surface enhanced Raman scattering

“…For example, tenascin-C is a glycoprotein that is expressed in the ECM of tissues during disease or injury, 18 and it is overexpressed in many cancer cell lines. 19 It can bind to cell surface receptors, such as toll-like receptor 4 (TLR4), which is present on stromal cells. 20 Furthermore, tenascin-C has been found in the stroma of solid tumours 21 and importantly, glioblastoma cells, such as U87-MG cells, are known to express high levels of tenascin-C. 22,23 By conjugating a peptide that can interact with tenascin-C to the surface of silver NPs, it was found that the NPs with the peptide were up taken by the U87 cells, while no uptake was observed with NPs lacking the peptide.…”