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Dissertation_FINAL for ETD 6-16-16.pdf (3.48 MB)

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Direct contact with perivascular tumor cells enhances integrin αvβ3 signaling and migration of endothelial cells

Burgett, Monica E
http://rave.ohiolink.edu/etdc/view?acc_num=kent1466174564

Abstract Details

2016, PHD, Kent State University, College of Arts and Sciences / School of Biomedical Sciences.
The secretion of soluble pro-angiogenic factors by tumor cells and stromal cells in the perivascular niche promotes the aggressive angiogenesis that is typical of glioblastoma (GBM). Here, we show that angiogenesis also can be promoted by a direct interaction between brain tumor cells, including tumor cells with cancer stem-like properties (CSCs), and endothelial cells (ECs). As shown in vitro, this direct interaction is mediated by binding of integrin αvβ3 expressed on ECs to the RGD-peptide in L1CAM expressed on CSCs. It promotes both EC network formation and enhances directed migration toward basic fibroblast growth factor. Activation of αvβ3 and bone marrow tyrosine kinase on chromosome X (BMX) is required for migration stimulated by direct binding but not for migration stimulated by soluble factors. RGD-peptide treatment of mice with established intracerebral GBM xenografts significantly reduced the percentage of Sox2-positive tumor cells and CSCs in close proximity to ECs, decreased integrin αvβ3 and BMX activation and p130CAS phosphorylation in the ECs, and reduced the vessel surface area. These results reveal a previously unrecognized aspect of the regulation of angiogenesis in GBM that can impact therapeutic anti-angiogenic targeting.
Candece Gladson, M.D. (Advisor)
Gail Fraizer, Ph.D. (Committee Member)
Derek Damron , Ph.D. (Committee Member)
Matthew Summers, Ph.D. (Committee Member)
Songping Huang, Ph.D. (Committee Member)
117 p.
Biomedical Research; Cellular Biology; Molecular Biology
endothelial cells; glioblastoma; angiogenesis; integrins; perivascular niche

Recommended Citations

Citations

  • Burgett, M. E. (2016). Direct contact with perivascular tumor cells enhances integrin αvβ3 signaling and migration of endothelial cells [Doctoral dissertation, Kent State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=kent1466174564

    APA Style (7th edition)

  • Burgett, Monica. Direct contact with perivascular tumor cells enhances integrin αvβ3 signaling and migration of endothelial cells. 2016. Kent State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=kent1466174564.

    MLA Style (8th edition)

  • Burgett, Monica. "Direct contact with perivascular tumor cells enhances integrin αvβ3 signaling and migration of endothelial cells." Doctoral dissertation, Kent State University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=kent1466174564

    Chicago Manual of Style (17th edition)

kent1466174564
1,091
© 2016, all rights reserved.
This open access ETD is published by Kent State University and OhioLINK.