Abstract:

Proteoglycans control numerous normal and pathological processes, among which are morphogenesis, tissue repair, inflammation, vascularization and cancer metastasis. During tumor development and growth, proteoglycan expression is markedly modified in the tumor microenvironment. Altered expression of proteoglycans on tumor and stromal cell membranes affects cancer cell signaling, growth and survival, cell adhesion, migration and angiogenesis. Despite the high complexity and heterogeneity of breast cancer, the rapid evolution in our knowledge that proteoglycans are among the key players in the breast tumor microenvironment suggests their potential as pharmacological targets in this type of cancer. It has been recently suggested that pharmacological treatment may target proteoglycan metabolism, their utilization as targets for immunotherapy or their direct use as therapeutic agents. The diversity inherent in the proteoglycans that will be presented herein provides the potential for multiple layers of regulation of breast tumor behavior. This review summarizes recent developments concerning the biology of selected proteoglycans in breast cancer, and presents potential targeted therapeutic approaches based on their novel key roles in breast cancer.

Notes:

Theocharis, Achilleas DSkandalis, Spyros SNeill, ThomasMulthaupt, Hinke A BHubo, MarioFrey, HelenaGopal, SandeepGomes, AngelicaAfratis, NikosLim, Hooi ChingCouchman, John RFilmus, JorgeSanderson, Ralph DSchaefer, LilianaIozzo, Renato VKaramanos, Nikos KengR01 CA138535/CA/NCI NIH HHS/R01 CA164462/CA/NCI NIH HHS/R01 CA138340/CA/NCI NIH HHS/R01 CA039481/CA/NCI NIH HHS/R01 CA120975/CA/NCI NIH HHS/R01 CA047282/CA/NCI NIH HHS/R01 CA47282/CA/NCI NIH HHS/R01 CA39481/CA/NCI NIH HHS/R01 CA 138535/CA/NCI NIH HHS/R01 CA38340/CA/NCI NIH HHS/P30 CA056036/CA/NCI NIH HHS/Research Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov'tReviewNetherlands2015/04/02Biochim Biophys Acta. 2015 Apr;1855(2):276-300. doi: 10.1016/j.bbcan.2015.03.006. Epub 2015 Mar 28.