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The role of heparins and nano-heparins as therapeutic tool in breast cancer

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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.

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Abbreviations

(EGFR):

epidermal growth factor receptor

(FGFR):

fibroblast growth factor receptor

(GAGs):

glycosaminoglycans

(HS):

heparan sulfate

(HSPGs):

heparan sulfate proteoglycans

(HER-2):

human epidermal growth factor receptor 2

(IGF-1R):

insulin-like growth factor receptor 1

(LMWH):

low molecular weight heparin

(LHT7):

LMWH-taurocholate conjugates

(LHT7-SAHA):

LHT7-suberoylanilide hydroxamic acid

(PGs):

proteoglycans

(LHTD4):

tetrameric deoxycholic acid

(UFH):

unfractionated heparin

(VEGFR):

vascular endothelial growth factor receptor

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Acknowledgment

This work was supported by the EU Horizon 2020 RISE action, GLYCANC project “Matrix glycans as multifunctional pathogenesis factors and therapeutic targets in cancer”, Ref. No. 645756.

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  1. Biochemistry, Biochemical Analysis and Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, 26110, Patras, Greece

    Nikos A. Afratis, Konstantina Karamanou, Zoi Piperigkou, Demitrios H. Vynios & Achilleas D. Theocharis

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  1. Nikos A. Afratis
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  2. Konstantina Karamanou
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  3. Zoi Piperigkou
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  4. Demitrios H. Vynios
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Afratis, N.A., Karamanou, K., Piperigkou, Z. et al. The role of heparins and nano-heparins as therapeutic tool in breast cancer. Glycoconj J 34, 299–307 (2017). https://doi.org/10.1007/s10719-016-9742-7

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