Skip to Main Content
 

Global Search Box

 
 
 

ETD Abstract Container

Abstract Header

Effect of alpha 2,6 Sialylation and Ionizing Radiation on Integrin-mediated Cell Adhesion and Cell Cycle Arrest

Abstract Details

2016, Doctor of Philosophy (PhD), Ohio University, Chemistry and Biochemistry (Arts and Sciences).
Cell adhesion is an important early step of cancer metastasis, yet the roles of sialylation in regulating integrin-mediated breast cancer cell adhesion in comparison to migration and invasion are not well-understood. The role of sialylation on alpha5 beta1 and alpha2 beta1 integrins in the regulation of adhesion between breast cancer cells and extracellular matrix (ECM) was studied. Our data showed that alpha2, alpha5 and beta1 integrins had considerable alpha 2,6 sialylation on MDA-MB-231 cells, whereas signals from MCF-7 cells were undetectable. Cleavage of alpha 2,6 sialylation increased adhesion of MDA-MB-231 cells to ECM, while adhesion of MCF-7 cells was unaffected, consistent with the latter’s lack of endogenous alpha 2,6 sialylated surface integrins. Neither surface expression of alpha5 beta1 and alpha2 beta1 integrins, nor activated beta 1 integrin, changed in MDA-MB-231 cells after sialidase treatment. However, sialidase treatment did not have significant impact on migration or invasion of MDA-MB-231 cells. Integrins not only play an important role in adhesion of cancer cells, but also have a direct connection with ionizing radiation-induced atherosclerosis, which is an adverse effect observed after radiotherapy. However, minimal attention has been given to monocytes/macrophages, which are exposed to the radiation at the same time. Under flow conditions using a parallel plate flow chamber to mimic physiological shear stress, we demonstrate here that the avidity between very late antigen-4 (VLA-4) of RAW264.7 cells and its ligand vascular cell adhesion molecule-1 (VCAM-1), was increased after low dose (0.5 Gy), but was reduced after higher dose (5 Gy) treatment of ionizing radiation. Treating the cells with free radical scavenger N-acetyl-L-cysteine reduced the avidity between RAW264.7 cells and VCAM-1 to a similar level. These results suggest that ionizing radiation regulates adhesive interactions between VLA-4 and VCAM-1, and that reactive oxygen species might function as a regulator, for this increased adhesiveness but with altered expression of integrin not play a major role. In addition to regulation of cell adhesion, ionizing radiation (IR) is known to induce cell cycle arrest which correlates with cell proliferation and cell death. Recent studies connect IR with endoplasmic reticulum (ER) stress, leading to activation of PKR-like endoplasmic reticulum kinase (PERK) and subsequent phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2a). However, the contribution of PERK and eIF2a phosphorylation in IR-induced G2/M arrest is incompletely understood. Here we report that IR-induced eIF2a phosphorylation was predominantly mediated by PERK and IR-induced G2/M arrest was blunted after totally abolishing eIF2a phosphorylation. Our results reveal that basal level of eIF2a phosphorylation is indispensable to maintain G2/M arrest in response to IR.
Shiyong Wu (Advisor)
113 p.

Recommended Citations

Citations

  • Yuan, Y. (2016). Effect of alpha 2,6 Sialylation and Ionizing Radiation on Integrin-mediated Cell Adhesion and Cell Cycle Arrest [Doctoral dissertation, Ohio University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1478556861213286

    APA Style (7th edition)

  • Yuan, Ye. Effect of alpha 2,6 Sialylation and Ionizing Radiation on Integrin-mediated Cell Adhesion and Cell Cycle Arrest. 2016. Ohio University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1478556861213286.

    MLA Style (8th edition)

  • Yuan, Ye. "Effect of alpha 2,6 Sialylation and Ionizing Radiation on Integrin-mediated Cell Adhesion and Cell Cycle Arrest." Doctoral dissertation, Ohio University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1478556861213286

    Chicago Manual of Style (17th edition)