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

• Main Authors: Priyamvada Pradeep, Yahya E. Choonara, Pradeep Kumar, Viness Pillay
• Format: Article
• Language: English
• Published: MDPI AG 2016-07-01
• Series: International Journal of Molecular Sciences
• Subjects: ovarian cancer; proteoglycans; crosslinked chondroitin sulphate; complexation; tumor proliferation; GD3G7 antibody; anti-VEGF
• Online Access: http://www.mdpi.com/1422-0067/17/7/1136

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.