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Evaluating CD47 Expression in Glioma Stem Cells as an immunotherapy approach

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2023, Master of Science (MS), Bowling Green State University, Biological Sciences.
Although there are many therapies against cancer, they involve devastating side effects. Hence, we need to understand the nature of cancer cells and the unique markers that exist within these cells that allow them to evade the immune system. These cell properties could be exploited to our advantage. CD47 is a cell membrane receptor protein widely expressed in most cells and is a versatile and crucial target in the tumor microenvironment for creating novel therapeutic approaches for cancer treatment. However, few studies have examined CD47 in glioma. CD47 is found on the surface of multiple cell types, and it usually protects the cells from being removed by phagocytes. It has been found that most cancer cells have high CD47 expression that prevents them from being engulfed by macrophages or activated microglial cells, essentially acting as a “don’t eat me signal.” A second protein expressed on cancer cells, calreticulin (CALR), facilitates cell removal by phagocytes, serving as an “eat me signal.” In this project, we compared CD47 expression in glioma cancer stem cells (CSCs), which are negative for Hoechst 33342 nuclear staining (H-), and non-stem glioma cells (Hoechst-positive, H+) of the C6 cell line derived from a rat astrocytoma. We examined the colocalization of CALR with CD47 in both C6 cell types using immunocytochemistry and compared CALR and CD47 gene expression reported in the NCI-60 database of multiple human cancers. We found a significant difference in CD47 expression, with more CD47 in the H+ cells than the H- cells, which could imply that GSCs are more susceptible to CD47 immunotherapy. The highest expression of CD47 ( 50% above signal range) appeared to be in exosomes related to both cell types. We found a positive correlation between CD47 and CALR distribution in the H+ cells (p = 0.0204) and in both H+ and H- cells combined (p = 0.0121), suggesting that the cells might protect themselves from CALR-induced phagocytosis by increasing CD47. We also discuss the possible role of circadian clock control of these two proteins. Our data help provide valuable insight into how these cells might evade detection and death by immune cells.
Michael Geusz, PhD (Committee Chair)
Julia Halo, PhD (Committee Member)
Paul Morris, PhD (Committee Member)
48 p.

Recommended Citations

Citations

  • Irshad, S. (2023). Evaluating CD47 Expression in Glioma Stem Cells as an immunotherapy approach [Master's thesis, Bowling Green State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1688747382930607

    APA Style (7th edition)

  • Irshad, Sana. Evaluating CD47 Expression in Glioma Stem Cells as an immunotherapy approach. 2023. Bowling Green State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1688747382930607.

    MLA Style (8th edition)

  • Irshad, Sana. "Evaluating CD47 Expression in Glioma Stem Cells as an immunotherapy approach." Master's thesis, Bowling Green State University, 2023. http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1688747382930607

    Chicago Manual of Style (17th edition)