Lubanska, Dorota

Porter, Lisa

Sorge, Alexandra

English

Scholarship at UWindsor

University of Windsor Scholarship at UWindsor UWill Discover Conference UWill Discover 2022 Control of Stemness in Glioma via Nanoparticle- Mediated Regulation of CD44 Receptor Alexandra Sorge University of Windsor, sorgea@uwindsor.ca Dorota Lubanska University of Windsor, Dorota.Lubanska@uwindsor.ca Lisa Porter University of Windsor, lporter@uwindsor.ca Follow this and additional works at: https://scholar.uwindsor.ca/uwilldiscover Sorge, Alexandra; Lubanska, Dorota; and Porter, Lisa, "Control of Stemness in Glioma via Nanoparticle- Mediated Regulation of CD44 Receptor" (2022). UWill Discover Conference. 17. https://scholar.uwindsor.ca/uwilldiscover/2022/2022Day1/17 This Event is brought to you for free and open access by the Conferences and Conference Proceedings at Scholarship at UWindsor. It has been accepted for inclusion in UWill Discover Conference by an authorized administrator of Scholarship at UWindsor. For more information, please contact scholarship@uwindsor.ca. 1Control of Stemness in Glioma via Nanoparticle-Mediated Regulation of CD44 Receptor Alexandra SorgeGlioblastoma (GBM)● Grade IV astrocytoma ● Most common and most aggressive malignant primary brain tumour ● Usually occur in cerebral hemispheres but can develop less commonly in other parts of the brain● Extremely poor prognosis, having around 15 months median survival rate23Tumour Initiating Cells (TICs) drive heterogeneity of  GBMCD44 Receptor- A transmembrane glycoprotein known for being a tumor initiating cell marker - CD44’s primary ligand is hyaluronic acid (HA)- The intracytoplasmic domain (ICD) of the CD44 receptor 4*Schema by Sami Alrashed56Investigating CD44 EssentialitySignificant decrease in proliferation in the shCD44 population in comparison to the pLKO control. The CD44 receptor is essential for cell proliferation.1.0000.338-0.2000.0000.2000.4000.6000.8001.0001.2001.4001.600pLKO shCD44RQ for CD44ShCD44 U-251Successful downregulation confirmed by Qrt-PCRpLKO U-2510500000100000015000002000000Day 0 Day 1 Day3 Day5Cell Count (cells/ml)Time CoursepLKOshCD44n=1 n=3CD44 knockdown changes Glioma cell morphologyCD44 Knockdown decrease proliferation of glioma cellsConjugated Polymer Nanoparticles (CPNs)○ CPNs are nanoparticles labeled with fluorescent HA, creating HA-CPNs that will specifically bind to CD44+ cells and provide potential theraputic effects○ Preliminary data shows downregulation of CD44+ cell proliferation and decreased tumor burden in GBM cell lines and patient derived xenografts with HA-CPN treatment 7CPNs decrease CD44+ cell proliferation*Figure by Fatima Nadeem8CD133 & CD44 TICs Downregulated with HA-CPNs  HA-CPN treatment targets the TIC marker population and selects for the population that do not have the TIC markers.n=3Clathrin-Mediated Endocytosis● Clathrin-mediated endocytosis(CME) is the mechanism of moving molecules across the cell surface to the interior via vesicles. *Figure by Sami Alrashed*Template by BioRender10CD44 protein expression levels are downregulated by HA-CPNs• Endosidin9 (En9) is a known inhibitor of clathrin-mediated endocytosis HA-CPN- mediate downregulation of CD44 is rescued by treatment with CME inhibitor*** **n=3 n=311Decreasing CD44+ TICs in GBM patient samplesPatient samples are significantly depleted in CD44+ cells when treated with HA-CPNsn=3 n=3 n=312Project Significance Acknowledgements• I’d like to thank Dr. Lisa Porter, Dr. Rondeau- Gagné and Dr. Dorota Lubanska, for your patience, guidance, and support during this project.• Thank you to Dr. Elizabeth Fidalgo da Silva and Flowcytometry facility for experimental support • Dr. Bre-Anne Fifield and lab mates for your assistance and encouragement in the lab.

Control of Stemness in Glioma via Nanoparticle- Mediated Regulation of CD44 Receptor

https://scholar.uwindsor.ca/cgi/viewcontent.cgi?article=1876&context=uwilldiscover

Control of Stemness in Glioma via Nanoparticle- Mediated Regulation of CD44 Receptor

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