Theocharis Achilleas D, Skandalis Spyros S, Neill Thomas, Multhaupt Hinke A B, Hubo Mario, Frey Helena, Gopal Sandeep, Gomes Angélica, Afratis Nikos, Lim Hooi Ching, Couchman John R, Filmus Jorge, Sanderson Ralph D, Schaefer Liliana, Iozzo Renato V, Karamanos Nikos K
Biochemistry, Biochemical Analysis & Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, 26500 Patras, Greece.
Department of Pathology, Anatomy and Cell Biology and the Cancer Cell Biology and Signaling Program, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Biochim Biophys Acta. 2015 Apr;1855(2):276-300. doi: 10.1016/j.bbcan.2015.03.006. Epub 2015 Mar 28.
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.
蛋白聚糖控制着众多正常和病理过程，其中包括形态发生、组织修复、炎症、血管生成和癌症转移。在肿瘤发生和生长过程中，肿瘤微环境中的蛋白聚糖表达会发生显著改变。肿瘤和基质细胞膜上蛋白聚糖表达的改变会影响癌细胞的信号传导、生长和存活、细胞黏附、迁移以及血管生成。尽管乳腺癌具有高度的复杂性和异质性，但我们对蛋白聚糖是乳腺肿瘤微环境关键参与者的认识迅速发展，这表明它们有可能成为这类癌症的药理学靶点。最近有人提出，药物治疗可以针对蛋白聚糖代谢、将其用作免疫治疗靶点或直接用作治疗剂。本文中将要介绍的蛋白聚糖所固有的多样性为乳腺肿瘤行为的多层调节提供了潜力。本综述总结了乳腺癌中特定蛋白聚糖生物学的最新进展，并基于它们在乳腺癌中的新关键作用提出了潜在的靶向治疗方法。
