Targeted therapeutic approaches primarily based on their novel key roles in breast cancer.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptKeywords proteoglycans; versican; decorin; biglycan; syndecans; glypicans; heparanase; serglycin; signaling; breast cancer1. Extracellular matrices in breast cancer: concentrate on the proteoglycans1.1. Breast cancer: a complex disease Breast cancer is a heterogeneous, tissue-specific disease, with substantial genotypic and phenotypic diversity. This kind of cancer prevails in women, although male breast cancer can also be observed. Estrogen receptor-alpha (ER), progesterone receptor (PgR), and epidermal development aspect receptor-2 (HER2) would be the 3 mandatory prognostic and predictive aspects in invasive breast cancer applied in routine clinical practice right now [1]. 4 main breast cancer subtypes drive therapy decisions: ER-positive and HER2-negative with a low or intermediate differentiation grade (luminal A); ER-positive and HER2-negative using a high differentiation grade (luminal B); aggressive kind of HER2-positive and triple-negative breast cancer (ER-, PgR- and HER2-negative). Two thirds of breast cancers are ERpositive. ER plays a crucial function within the improvement, progression and therapy of breast cancer and is of specific interest simply because its TNF Receptor Superfamily Proteins Source protein level is elevated in premalignant and malignant breast lesions, but not in normal tissue. For that reason, ER can be a important predictive and prognostic aspect inside the clinical management of breast cancer. Nonetheless, the majority of hormonally responsive breast cancers create resistance to anti-estrogen therapy and progress to a far more aggressive and hormonally independent phenotype. Quite a few preclinical and clinical studies carried out until todays are primarily focused on genetic components involved in tumor progression and tumor microenvironment as to far better realize the biology of breast tumor cells and improve breast cancer treatment. 1.2. Proteoglycans: essential molecular effectors of breast cancer cell surface and pericellular microenvironments Interactions of cancer cells using the tumor microenvironment are vital determinants of cancer progression toward metastasis. The tumor microenvironment contains several distinct cell varieties, such as endothelial cells and their precursors, pericytes, smooth muscle cells, fibroblasts, cancer/tumor-associated fibroblasts (CAFs/TAFs), myofibroblasts, and inflammatory cells [2]. These cells are immersed in very dynamic and functional extracellular matrices (ECMs) composed by macromolecules, like proteoglycans (PGs), collagen, laminin, fibronectin and proteinases. PGs are important elements of ECMs too as the cell surfaces. They may be composed of a certain core protein substituted with 1 or far more covalently linked glycosaminoglycan (GAG) chains resulting in higher degree of structural and functional complexity. GAGs (chondroitin sulfate, CS; dermatan sulfate, DS; heparan sulfate, HS; heparin, HP) are linear heteropolysaccharides composed of repeating disaccharides of hexosamines (N-acetyl-galactosamine or N-acetyl-glucosamine) and uronicBiochim Biophys Acta. Author manuscript; obtainable in PMC 2016 April 01.Theocharis et al.Pageacids (D-glucuronic acid or L-iduronic acid) which can be being sulfated at many positions. Keratan sulfate (KS) is composed of repeating disaccharides containing IL-22 Receptor Proteins Storage & Stability N-acetylglucosamine and galactose [3]. Notably, hyaluronan (HA) may be the only GAG that may be not covalently bound to PG core protein.