Roles of Proteoglycans and Glycosaminoglycans in Cancer Development and Progression

Abstract

The extracellular matrix (ECM) spatiotemporally controls cell fate; however, dysregulation of ECM remodeling can lead to tumorigenesis and cancer development by providing favorable conditions for tumor cells. Proteoglycans (PGs) and glycosaminoglycans (GAGs) are the major macromolecules composing ECM. They influence both cell behavior and matrix properties through direct and indirect interactions with various cytokines, growth factors, cell surface receptors, adhesion molecules, enzymes, and glycoproteins within the ECM. The classical features of PGs/GAGs play well-known roles in cancer angiogenesis, proliferation, invasion, and metastasis. Several lines of evidence suggest that PGs/GAGs critically affect broader aspects in cancer initiation and the progression process, including regulation of cell metabolism, serving as a sensor of ECM’s mechanical properties, affecting immune supervision, and participating in therapeutic resistance to various forms of treatment. These functions may be implemented through the characteristics of PGs/GAGs as molecular bridges linking ECM and cells in cell-specific and context-specific manners within the tumor microenvironment (TME). In this review, we intend to present a comprehensive illustration of the ways in which PGs/GAGs participate in and regulate several aspects of tumorigenesis; we put forward a perspective regarding their effects as biomarkers or targets for diagnoses and therapeutic interventions.

Platelets, Constant and Cooperative Companions of Sessile and Disseminating Tumor Cells, Crucially Contribute to the Tumor Microenvironment

“…Together, they form the scaffold, which keeps the tissue in shape and provides a stiff collagenous capsule of desmoplastic tumors (Leight et al, 2017;Mohammadi and Sahai, 2018;Martins Cavaco et al, 2020). Moreover, the ECM scaffold tethers growth factors, forming the morphogenic stage for cell differentiation (Lodyga and Hinz, 2020;Wei et al, 2020). Also the presence of metabolic components, such as protons, lactate, reactive oxygen species (ROS), contribute to the typical environment of cancer cells in a solid tumor mass (Oudin and Weaver, 2016).…”

Analytical Performance of a Standardized Kit for Mass Spectrometry-based Measurements of Human Glycosaminoglycans

“…GAGs are increasingly recognized as key molecular actors in mechanisms central to human physiology and pathology such as structural support within the extracellular matrix and regulation of cell signaling ( 2, 24 ). These mechanisms ultimately control phenotypes that, in disease, can culminate in physical and mental disabilities in mucopolysaccharidosis ( 4 ), jeopardize wound healing ( 25 ), promote cancer ( 26 ), lead to respiratory failure ( 3 ), or enable binding of viruses such as SARS-CoV-2 ( 10 ). GAGs have therefore been proposed as potential biomarkers for these different diseases ( 4, 27, 28 ).…”

Regulatory VCAN Polymorphism is Associated with Shoulder Pain and Disability in Breast Cancer Survivors

“…This may re ect, at least in part, the role of proteoglycans in the development and progression of cancer, thereby, in uencing treatment options and selections. Although, no studies to date have demonstrated their roles in breast cancer, BGN and DCN have been implicated in the development and progression of endometrial, bladder, colon, blood or lung cancers [42].…”