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Emily Crowe Thesis 8-5-22 Final.pdf (1.46 MB)

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Osteocytic PPARG Supports Prostate Cancer Growth in Bone

Crowe, Emily
http://rave.ohiolink.edu/etdc/view?acc_num=mco1659703899258599

Abstract Details

2022, Master of Science in Biomedical Sciences (MSBS), University of Toledo, Biomedical Sciences (Molecular Medicine).
Bone, the most common site of prostate cancer (PCa) metastasis, provides a favorable microenvironment for malignant cancers to grow. Previous studies have focused on two bone remodeling cells, osteoclasts, and osteoblasts, concerning PCa colonization and proliferation at skeletal sites. However, little is known about the most abundant cells in this process, osteocytes (OTs). Observed here osteocytic peroxisome proliferator-activated receptor gamma (PPARG) protein plays an important role in the tumor growth and bone destructive phenotype of PCa bone metastasis. Tibias of WT mice injected with PCa cells (RM-1) displayed tumor burdens, bone destruction, and loss of marrow adiposity. In contrast, mice with osteocyte-specific deletion of PPARG (Dmp1CrePparℽflfl or ℽOTKO) were protected from these effects. Transwell-coculture (CC) experiments of CRISPR/Cas9 PPARG-edited osteocytic MLO-Y4 (Y4-γKO) cells with PCa cell lines revealed that expression of prostaglandin E2 (PGE2)-producing enzyme, PGES, decreased in OTs deficient in PPARG. Moreover, proliferation assays using CM-CC collected from Y4-γKO cells indicated a decreased RM-1 (PCa cell line) cell growth rate as compared to CM-CC collected from unedited MLO-Y4 cells. Indeed, cytokine array and ELISA analyses of conditioned media collected from Y4-γKO cells grown in CC conditions with RM-1 or PC3 cells (CM-CC) cells revealed a reduction in chemokine and cytokine factors, CXCL5 and GDF-15, which have been found to support PCa cell proliferation. These findings suggest that osteocytic PPARG controls tumor growth and bone destruction in PCa bone metastasis. Therefore, osteocytic PPARG, as a pertinent pharmacological target, should be considered for the treatment of PCa in bone.
Beata Lecka-Czernik (Advisor)
Jennifer Hill (Committee Member)
Xiaohong Li (Committee Member)
65 p.
Biomedical Research; Medicine; Molecular Biology; Oncology
osteocytes; PPARG; prostate cancer; GDF-15; CXCL5; PGES; PGE2; bone metastasis; bone microenvironment;

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Citations

  • Crowe, E. (2022). Osteocytic PPARG Supports Prostate Cancer Growth in Bone [Master's thesis, University of Toledo]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=mco1659703899258599

    APA Style (7th edition)

  • Crowe, Emily. Osteocytic PPARG Supports Prostate Cancer Growth in Bone. 2022. University of Toledo, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=mco1659703899258599.

    MLA Style (8th edition)

  • Crowe, Emily. "Osteocytic PPARG Supports Prostate Cancer Growth in Bone." Master's thesis, University of Toledo, 2022. http://rave.ohiolink.edu/etdc/view?acc_num=mco1659703899258599

    Chicago Manual of Style (17th edition)

mco1659703899258599
95
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This open access ETD is published by University of Toledo Health Science Campus and OhioLINK.