Chondroitin Sulphate Proteoglycans in the Tumour Microenvironment

Mellai, Marta; Casalone, Cristina; Corona, Cristiano; Favole, Adriano; Cassoni, Paola; Schiffer, Davide; Boldorini, Renzo

doi:10.1007/978-3-030-48457-6_5

Cited by 25 publications

(15 citation statements)

References 129 publications

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“…Protein kinase N2 (PKN2) is a serine / threonine protein kinase associated with PKC. It plays an important role in transcription activation, cell cycle, cell adhesion, and migration 27,28 . Koh H's research indicated that the C‐terminal region of PKN2 can interact with Akt, inhibit threonine phosphorylation at 308 and 473 site of Akt, and specifically downregulate the activity of Akt protein kinase, blocking the activity of AKT signaling pathway and promoting tumor cell apoptosis 29 .…”

Section: Discussionmentioning

confidence: 99%

Identification of a 9‐gene prognostic signature for breast cancer

et al. 2020

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BRCA is the most common cancer in women. The 2018 GLOBOCAN report disclosed that approximately 2.1 million women worldwide were diagnosed with BRCA in 2018, accounting for one-fourth of all cancer cases among women. 1 According to clinicopathological criteria, BRCA is divided into four subtypes Luminal A, Luminal B, Erb-B2 overexpression, and Basal-like, represents a convenient approximation. 2 Ihemelandu study indicated that Luminal A type accounts for 50% of BRCA patients, Luminal B, Erb-B2 overexpression, and Basal-like subtypes accounted for 14.1%, 12.7%, and 23.2%, respectively. 3 For ER receptor-positive BRCA, tamoxifen, and aromatase inhibitors are effective endocrine therapies. 4 For HER2-positive BRCA, the monoclonal antibody trastuzumab and lapatinib have been approved as the most specific molecular targeting drugs. 5,6 With the development of medical technology, the prognosis of BRCA has been

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Section: Discussionmentioning

confidence: 99%

Identification of a 9‐gene prognostic signature for breast cancer

et al. 2020

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“…Functionally similarly versatile are glycosaminoglycans (GAGs), and the proteinand sulfate-free hyaluronic acid (HA) made up of N-acetylglucosamine and glucuronic acid [46,47], as well as sulfated GAG-chain containing proteoglycans, such as heparan sulfate and keratan sulfate, and galactosamine-containing chondroitin sulfate and dermatan sulfate [4,5,48,49]. According to their location, proteoglycans are divided into extracellular, membrane-bound, and intracellular proteoglycans.…”

Section: The Extracellular Matrix As a Key Component Of The Tmementioning

confidence: 99%

“…The extracellular group includes the hyaluronic acid-binding hyalectans (e.g., aggrecan, versican with four different splice variants, neurocan, and brevican), the small leucine-rich proteoglycans (SLRPs, e.g., decorin, biglycan, fibromodulin, and lumican), and the BM-located pericellular proteoglycans (e.g., perlecan, agrin, and collagen XVIII). Perlecan, agrin, and the network-forming type VIII collagen bear heparan sulfate GAG chains [48], while the hyalectans and SLRPs are decorated with different numbers of covalently attached chondroitin sulfate, sometimes in combination with additional dermatan sulfate chains (decorin) or keratan sulfate chains (aggrecan, fibromodulin, lumican) [49]. The extracellular proteoglycans non-covalently link up with the scaffold of fibril-forming ECM components in different ways.…”

Section: The Extracellular Matrix As a Key Component Of The Tmementioning

confidence: 99%

“…Furthermore, membrane-bound proteoglycans, such as syndecans, glypicans, and betaglycan, influence interactions between cancer cells and the TME [50]. Notably, the expression of the transmembrane proteoglycan NG2 (CSPG4) is altered on cancer cells and CAFs and may serve as a CAF-marker [49]. The mode of action of membrane-bound proteoglycans is diverse.…”

Section: The "Give and Take" Between The Ecm And Cells Within The Tmementioning

confidence: 99%

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Hold on or Cut? Integrin- and MMP-Mediated Cell–Matrix Interactions in the Tumor Microenvironment

Niland

Eble

2020

IJMS

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The tumor microenvironment (TME) has become the focus of interest in cancer research and treatment. It includes the extracellular matrix (ECM) and ECM-modifying enzymes that are secreted by cancer and neighboring cells. The ECM serves both to anchor the tumor cells embedded in it and as a means of communication between the various cellular and non-cellular components of the TME. The cells of the TME modify their surrounding cancer-characteristic ECM. This in turn provides feedback to them via cellular receptors, thereby regulating, together with cytokines and exosomes, differentiation processes as well as tumor progression and spread. Matrix remodeling is accomplished by altering the repertoire of ECM components and by biophysical changes in stiffness and tension caused by ECM-crosslinking and ECM-degrading enzymes, in particular matrix metalloproteinases (MMPs). These can degrade ECM barriers or, by partial proteolysis, release soluble ECM fragments called matrikines, which influence cells inside and outside the TME. This review examines the changes in the ECM of the TME and the interaction between cells and the ECM, with a particular focus on MMPs.

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“…Brain tissue ECM represents a unique structure, mainly composed of proteoglycans (PGs) and glycosaminoglycans (GAGs), which involvement in normal physiology and carcinogenesis is extensively studied for different cancers (21,22). The important role of PGs in brain carcinogenesis is comprehensively discussed in the recent reviews (23)(24)(25), with special attention to chondroitin sulfate proteoglycans (CSPGs) (26,27) and CSPG4 (28), heparan sulfate proteoglycans (HSPGs) (29), and polysaccharide molecules of heparan sulfate (HS) (30)(31)(32) and keratan sulfates (KS) (33). As for GAGs, one of the most abundant GAGs in brain ECM is hyaluronan (HA), which has a functional role in the GBM development and is comprehensively described in the recent review by Pibuel et al (34).…”

Section: Introductionmentioning

confidence: 99%

Chemotherapy-Induced Degradation of Glycosylated Components of the Brain Extracellular Matrix Promotes Glioblastoma Relapse Development in an Animal Model

et al. 2021

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Adjuvant chemotherapy with temozolomide (TMZ) is an intrinsic part of glioblastoma multiforme (GBM) therapy targeted to eliminate residual GBM cells. Despite the intensive treatment, a GBM relapse develops in the majority of cases resulting in poor outcome of the disease. Here, we investigated off-target negative effects of the systemic chemotherapy on glycosylated components of the brain extracellular matrix (ECM) and their functional significance. Using an elaborated GBM relapse animal model, we demonstrated that healthy brain tissue resists GBM cell proliferation and invasion, thereby restricting tumor development. TMZ-induced [especially in combination with dexamethasone (DXM)] changes in composition and content of brain ECM proteoglycans (PGs) resulted in the accelerated adhesion, proliferation, and invasion of GBM cells into brain organotypic slices ex vivo and more active growth and invasion of experimental xenograft GBM tumors in SCID mouse brain in vivo. These changes occurred both at core proteins and polysaccharide chain levels, and degradation of chondroitin sulfate (CS) was identified as a key event responsible for the observed functional effects. Collectively, our findings demonstrate that chemotherapy-induced changes in glycosylated components of brain ECM can impact the fate of residual GBM cells and GBM relapse development. ECM-targeted supportive therapy might be a useful strategy to mitigate the negative off-target effects of the adjuvant GBM treatment and increase the relapse-free survival of GBM patients.

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Chondroitin Sulphate Proteoglycans in the Tumour Microenvironment

Cited by 25 publications

References 129 publications

Identification of a 9‐gene prognostic signature for breast cancer

Identification of a 9‐gene prognostic signature for breast cancer

Hold on or Cut? Integrin- and MMP-Mediated Cell–Matrix Interactions in the Tumor Microenvironment

Chemotherapy-Induced Degradation of Glycosylated Components of the Brain Extracellular Matrix Promotes Glioblastoma Relapse Development in an Animal Model

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