title: The role of heparins and nano-heparins as therapeutic tool in breast cancer.
abstract: Glycosaminoglycans are integral part of the dynamic extracellular matrix (ECM) network that control crucial biochemical and biomechanical signals required for tissue morphogenesis, differentiation, homeostasis and cancer development. Breast cancer cells communicate with stromal ones to modulate ECM mainly through release of soluble effectors during cancer progression. The intracellular cross-talk between cell surface receptors and estrogen receptors is important for the regulation of breast cancer cell properties and production of ECM molecules. In turn, reorganized ECM-cell surface interface modulates signaling cascades, which regulate almost all aspects of breast cell behavior. Heparan sulfate chains present on cell surface and matrix proteoglycans are involved in regulation of breast cancer functions since they are capable of binding numerous matrix molecules, growth factors and inflammatory mediators thus modulating their signaling. In addition to its anticoagulant activity, there is accumulating evidence highlighting various anticancer activities of heparin and nano-heparin derivatives in numerous types of cancer. Importantly, heparin derivatives significantly reduce breast cancer cell proliferation and metastasis in vitro and in vivo models as well as regulates the expression profile of major ECM macromolecules, providing strong evidence for therapeutic targeting. Nano-formulations of the glycosaminoglycan heparin are possibly novel tools for targeting tumor microenvironment. In this review, the role of heparan sulfate/heparin and its nano-formulations in breast cancer biology are presented and discussed in terms of future pharmacological targeting.
authors: Biochemistry, Biochemical Analysis and Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, 26110, Patras, Greece.
authors: Nikos A
authors: NA
authors: Afratis
authors: Biochemistry, Biochemical Analysis and Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, 26110, Patras, Greece.
authors: Konstantina
authors: K
authors: Karamanou
authors: Biochemistry, Biochemical Analysis and Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, 26110, Patras, Greece.
authors: Zoi
authors: Z
authors: Piperigkou
authors: Biochemistry, Biochemical Analysis and Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, 26110, Patras, Greece.
authors: Demitrios H
authors: DH
authors: Vynios
authors: Biochemistry, Biochemical Analysis and Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, 26110, Patras, Greece. atheoch@upatras.gr.
authors: Achilleas D
authors: AD
authors: Theocharis
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002450:Cell Communication / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006493:Heparin / Q000737:chemistry* / Q000627:therapeutic use; D006497:Heparan Sulfate / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D015398:Signal Transduction; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D016207:Cytokines; D006493:Heparin; D006497:Heparan Sulfate; D036341:Intercellular Signaling Peptides and Proteins
keywords: Breast cancer; Heparan sulfate; Heparin; Nano heparin; Pharmacological targeting