Heparan sulfate proteoglycans (HSPGs) have crucial regulatory roles in tumor onset and progression. HSPGs

are composed of a core protein and glycan chains characterized by repeated disaccharide units which can

be sulfated at different amount and position. HSPG have enormous structural diversity due to the different

possible modifications of the single saccharide units within the polysaccharide, such as position, sulphation

and acetylation. As a result HSPG can bind and modulate their binding to signaling molecules such as

growth factors, morphogens and chemokines1 .

HSPG proved to be important in mediating cancer development and progression by enhancing the binding

of growth factors, morphogens and cytokines to their cognate receptors, thus activating signaling pathways

that give rise to angiogensis, cell growth and proliferation, together with invasion and metastasis 2-3.

NT4 is a branched peptides that targets HSPGs. NT4 specifically binds to sulfated glycosaminoglycans on

cancer cells and tissues. NT4 can be conjugated to many different cytotoxic units and tracers. NT4

conjugated to paclitaxel produced tumor regression in a breast cancer orthotopic mouse model 4. NT4

conjugated to tracers can discriminate between tumor and healthy tissue in different human cancer

specimen5.

We will show the ability of NT4 to drive tracers onto tumor lesions by means of Qdots and in vivo imaging,

proving their promising features as theranostics. We will also show NT4 ability to interfere with HSPG-

modulated activities such as: tumor cell proliferation, migration and invasion of matrix; as well as

endothelial cells proliferation, migration and tube formation. NT4-HSPG interactions and consequent

modulation of signaling pathways will prove the importance of this versatile tool, NT4, in addressing tumor

cells and interfering in their cell-cell and cell-matrix communications.

Bibliography

1. Gharbaran R. et al. Tumour Biol. 2016; 37:11573-11588.

2. Purushothaman A et al. Blood. 2010; 115:2449-57.

3. Lee JH et al. J Biol Chem. 2009; 284:27167-75.

4. Brunetti, J. et al. Scientific Reports. DOI:10.1038/srep17736

5. Falciani C. et al. J Med Chem. 2013; 56:5009-18.

Citation Format: Chiara Falciani, Jlenia Brunetti, Lorenzo Depau, Alessandro Pini, Giulia Riolo, Elisabetta Mandarini, Luisa Bracci. Heparan sulfate proteoglycans as novel target in cancer precise therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1153. doi:10.1158/1538-7445.AM2017-1153