Formulation and Implementation of CRISPR Edited Glioblastoma Cells to Evaluate Triplatin-Proteoglycan Interactions

Location

CSU Ballroom

Start Date

2-4-2019 10:00 AM

End Date

2-4-2019 11:30 AM

Student's Major

Chemistry and Geology

Student's College

Science, Engineering and Technology

Mentor's Name

Samantha Katner

Mentor's Department

Chemistry and Geology

Mentor's College

Science, Engineering and Technology

Description

Proteoglycans are ubiquitous protein/carbohydrate complexes that are found on cell surfaces. They are able to regulate cell growth and vascularization, processes that are exploited by cancer cells. Heparanase, an enzyme that cleaves glypicans, can alter the structure of proteoglycans and change their bioactivity. These enzymes are overexpressed in glioblastomas and are thought to contribute to the rapid and aggressive growth of cancer. Recently, Triplatin, a polynuclear platinum complex (PPC), interacts with heparan sulfate proteoglycans (HSPGs), and thus inhibits heparanase cleavage and growth factor-proteoglycan-mediated signaling. Moreover, previous studies have demonstrated Triplatin's potent cytotoxicity in glioblastoma mouse models that may also be explained by glycan targeting in these tumors. This relationship remains incompletely elucidated. Here, we generate glypican-3 (GPC3, a HSPG) knockout glioblastoma cells using CRISPR editing with number 31 sgRNA. To verify the knockout, we use western blotting and genomic analyses. We compare Triplatin cytotoxicity in wild-type to CRISPR edited glioblastoma cells. Further, we examine Triplatin activity in patient-derived glioblastoma cell line panel and compare it to other PPCs. The further exploration of PPC selectivity for HSPGs could allow for tailored chemotherapeutic treatment to patients with glioblastoma and may pave the way for new molecular targets and more effective treatment for glial tumors in the future.

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Apr 2nd, 10:00 AM Apr 2nd, 11:30 AM

Formulation and Implementation of CRISPR Edited Glioblastoma Cells to Evaluate Triplatin-Proteoglycan Interactions

CSU Ballroom

Proteoglycans are ubiquitous protein/carbohydrate complexes that are found on cell surfaces. They are able to regulate cell growth and vascularization, processes that are exploited by cancer cells. Heparanase, an enzyme that cleaves glypicans, can alter the structure of proteoglycans and change their bioactivity. These enzymes are overexpressed in glioblastomas and are thought to contribute to the rapid and aggressive growth of cancer. Recently, Triplatin, a polynuclear platinum complex (PPC), interacts with heparan sulfate proteoglycans (HSPGs), and thus inhibits heparanase cleavage and growth factor-proteoglycan-mediated signaling. Moreover, previous studies have demonstrated Triplatin's potent cytotoxicity in glioblastoma mouse models that may also be explained by glycan targeting in these tumors. This relationship remains incompletely elucidated. Here, we generate glypican-3 (GPC3, a HSPG) knockout glioblastoma cells using CRISPR editing with number 31 sgRNA. To verify the knockout, we use western blotting and genomic analyses. We compare Triplatin cytotoxicity in wild-type to CRISPR edited glioblastoma cells. Further, we examine Triplatin activity in patient-derived glioblastoma cell line panel and compare it to other PPCs. The further exploration of PPC selectivity for HSPGs could allow for tailored chemotherapeutic treatment to patients with glioblastoma and may pave the way for new molecular targets and more effective treatment for glial tumors in the future.

Recommended Citation

Pitcher, Morgan and Tehut Zewdu. "Formulation and Implementation of CRISPR Edited Glioblastoma Cells to Evaluate Triplatin-Proteoglycan Interactions." Undergraduate Research Symposium, Mankato, MN, April 2, 2019.
https://cornerstone.lib.mnsu.edu/urs/2019/poster-session-A/35