Cell-surface heparan sulfate proteoglycans as multifunctional integrators of signaling in cancer

Hassan, Nourhan; Greve, Burkhard; Espinoza-Sánchez, Nancy Adriana; Götte, Martin

doi:10.1016/j.cellsig.2020.109822

Cited by 84 publications

(103 citation statements)

References 280 publications

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“…Given the many essential cellular and developmental processes in which HS and HSPGs are involved, it is expected that modifications in HSPG expression and structure contribute to a dysregulation in function and lead to pathological scenarios, such as cancer [12,17]. In Section 4, we address several cancer cellular features that are regulated by changes in expression, glycosylation and sulfation profiles of HSPGs, which in turn translate into cancer progression.…”

Section: In Physiologymentioning

confidence: 99%

“…Over the last decade, new insights have emerged regarding the mechanisms and the biological significance of those interactions [7,[11][12][13], and in this last couple of years, their biomedical potential has been at the forefront in glycobiology translational research [14][15][16]. HS interfere in many steps of tumour progression, such as cancer cell proliferation, immune response escaping, invasion of neighbour tissues and metastasis [7,9,17]. Moreover, the aberrant expression of different HSPGs and of the key enzymes involved in HS biosynthesis and post-synthesis modifications impact cancer cell behaviour [17,18].…”

Section: Introductionmentioning

confidence: 99%

“…HS interfere in many steps of tumour progression, such as cancer cell proliferation, immune response escaping, invasion of neighbour tissues and metastasis [7,9,17]. Moreover, the aberrant expression of different HSPGs and of the key enzymes involved in HS biosynthesis and post-synthesis modifications impact cancer cell behaviour [17,18]. The interplay between researchers and clinicians has been key to identify the major needs in the clinical practice, and therefore, propel a better understanding on the potential of HS with the ultimate goal of improving cancer patients' management.…”

Section: Introductionmentioning

confidence: 99%

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Heparan Sulfate Glycosaminoglycans: (Un)Expected Allies in Cancer Clinical Management

et al. 2021

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In an era when cancer glycobiology research is exponentially growing, we are witnessing a progressive translation of the major scientific findings to the clinical practice with the overarching aim of improving cancer patients’ management. Many mechanistic cell biology studies have demonstrated that heparan sulfate (HS) glycosaminoglycans are key molecules responsible for several molecular and biochemical processes, impacting extracellular matrix properties and cellular functions. HS can interact with a myriad of different ligands, and therefore, hold a pleiotropic role in regulating the activity of important cellular receptors and downstream signalling pathways. The aberrant expression of HS glycan chains in tumours determines main malignant features, such as cancer cell proliferation, angiogenesis, invasion and metastasis. In this review, we devote particular attention to HS biological activities, its expression profile and modulation in cancer. Moreover, we highlight HS clinical potential to improve both diagnosis and prognosis of cancer, either as HS-based biomarkers or as therapeutic targets.

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Section: In Physiologymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Heparan Sulfate Glycosaminoglycans: (Un)Expected Allies in Cancer Clinical Management

et al. 2021

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“…The mode of action of membrane-bound proteoglycans is diverse. In addition to tethering growth factors, such as TGF-β, VEGF, and hepatocyte growth factor (HGF), they act as co-receptors too [76][77][78]. Betaglycan is also known as TGF-β type III receptor [5].…”

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

confidence: 99%

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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“…The influence of PGs has also been widely documented in other pathologies [2]. In cancer, PGs contribute to the generation of a profoundly remodeled ECM during tumorigenesis [8][9][10], but they can also act as pleiotropic modulators of different signaling pathways [11]. Cancer-associated fibroblasts are mainly responsible for those changes.…”

Section: Introductionmentioning

confidence: 99%

Hyalectanase Activities by the ADAMTS Metalloproteases

Fontanil

Mohamedi

Casado

et al. 2021

IJMS

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The hyalectan family is composed of the proteoglycans aggrecan, versican, brevican and neurocan. Hyalectans, also known as lecticans, are components of the extracellular matrix of different tissues and play essential roles in key biological processes including skeletal development, and they are related to the correct maintenance of the vascular and central nervous system. For instance, hyalectans participate in the organization of structures such as perineural nets and in the regulation of neurite outgrowth or brain recovery following a traumatic injury. The ADAMTS (A Disintegrin and Metalloprotease domains, with thrombospondin motifs) family consists of 19 secreted metalloproteases. These enzymes also perform important roles in the structural organization and function of the extracellular matrix through interactions with other matrix components or as a consequence of their catalytic activity. In this regard, some of their preferred substrates are the hyalectans. In fact, ADAMTSs cleave hyalectans not only as a mechanism for clearance or turnover of proteoglycans but also to generate bioactive fragments which display specific functions. In this article we review some of the physiological and pathological effects derived from cleavages of hyalectans mediated by ADAMTSs.

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Cell-surface heparan sulfate proteoglycans as multifunctional integrators of signaling in cancer

Cited by 84 publications

References 280 publications

Heparan Sulfate Glycosaminoglycans: (Un)Expected Allies in Cancer Clinical Management

Heparan Sulfate Glycosaminoglycans: (Un)Expected Allies in Cancer Clinical Management

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

Hyalectanase Activities by the ADAMTS Metalloproteases

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