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Int. J. Mol. Sci. 2016, 17(7), 1136; doi:10.3390/ijms17071136

“On-The-Spot” Arresting of Chondroitin Sulphate Proteoglycans: Implications for Ovarian Adenocarcinoma Recognition and Intervention

Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown 2193, South Africa
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Academic Editor: Sanjay K. Srivastava
Received: 27 May 2016 / Revised: 7 July 2016 / Accepted: 12 July 2016 / Published: 18 July 2016
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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Abstract

Ovarian Cancer (OC) is one of the leading causes of cancer-associated death among women. The underlying biochemical cause of OC proliferation is usually attributed to the over-expression of Chondroitin Sulphate Proteoglycans (CSPGs) wherein the CS-E subgroup plays a major role in tumor cell proliferation by over-expressing vascular endothelial growth factor (VEGF). We hereby hypothesize that by targeting the OC extracellular matrix using a CS-E-specific antibody, GD3G7, we could provide spatial delivery of crosslinkers and anti-VEGF agents to firstly induce in vivo crosslinking and complexation (arresting) of CS-E into a “biogel mass” for efficient and effective detection, detachment and reduction of tumorous tissue, and secondly inhibit angiogenesis in OC. It is further proposed that the antibody-assisted targeted delivery of CS-E crosslinkers can bind to highly anionic CS-E to form a polyelectrolyte complex to inhibit the formation of ovarian tumor spheroids that are responsible for spheroid-induced mesothelial clearance and progression of OC. The hypothesis also describes the potential in vivo “On-The-Spot” CSPG crosslinkers such as sodium trimetaphosphate (physical crosslinker), 1,12-diaminododecane (chemical crosslinker), poly(ethylene glycol) diglycidyl ether (synthetic polymer), and chitosan (natural polyelectrolyte-forming agent). In conclusion, this hypothesis proposes in vivo spatial crosslinking of CSPGs as a potential theranostic intervention strategy for OC—a first in the field of cancer research. View Full-Text
Keywords: ovarian cancer; proteoglycans; crosslinked chondroitin sulphate; complexation; tumor proliferation; GD3G7 antibody; anti-VEGF ovarian cancer; proteoglycans; crosslinked chondroitin sulphate; complexation; tumor proliferation; GD3G7 antibody; anti-VEGF
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Pradeep, P.; Choonara, Y.E.; Kumar, P.; Pillay, V. “On-The-Spot” Arresting of Chondroitin Sulphate Proteoglycans: Implications for Ovarian Adenocarcinoma Recognition and Intervention. Int. J. Mol. Sci. 2016, 17, 1136.

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