Publication Date
2018
Document Type
Thesis
Committee Members
Ji Chen Bihl (Committee Member), Yanfang Chen (Advisor), Ravi P. Sahu (Committee Member)
Degree Name
Master of Science (MS)
Abstract
Multiple myeloma is a hematological malignancy characterized by clonal proliferation of plasma cells generally caused by chromosomal abnormalities. It occurs in the bone marrow, which is the microenvironment of multiple myeloma. Exosomes (EXs) are 30-100 nm membrane-derived micro-vesicles containing various of bioactive molecules, such as microRNAs, to mediate the cell-cell interaction. Numerous studies reported that exosomes play a significant role in tumor microenvironment. Angiogenesis has the important implication in tumor exacerbation to supply nutrients to promote the progression of cancer cells through endothelial cells (ECs). Some studies demonstrated that microRNA-29b (miR-29b) can suppress tumor development and inhibit angiogenesis. Therefore, in this study, we designed experiments to research the relationship between exosomes released from multiple myeloma, miR-29b and angiogenesis in ECs. Two types of multiple myeloma cells, OPM2 and RPMI-8226 cell lines, were treated with C6-Ceramide. Their released exosomes (MM-EXC6-Cer) were collected, which enriched in miR-29b. MM-EXC6-Cer were cocultured with human umbilical vein endothelial cells (HUVECs) to test the effect on angiogenic function of HUVEC. The results showed that the EC proliferation, the tube formation, migration and vascular endothelial growth factor A (VEGFA) expression were decreased in ECs. In addition, miR-29b inhibitor was used in ECs, and could decrease the level of the miR-29b in ECs. Exosomes released from multiple myeloma cells (MM-EX) were cocultured with ECs, which were treated with miR-29b inhibitor, to examine the effects on EC angiogenic function. We found that EC proliferation, VEGFA expression, migration and tube formation were promoted. This data demonstrated that miR-29b can negatively modulate the angiogenic function of ECs through exosomes secreted by multiple myeloma cells.
Page Count
57
Department or Program
Department of Pharmacology and Toxicology
Year Degree Awarded
2018
Copyright
Copyright 2018, some rights reserved. My ETD may be copied and distributed only for non-commercial purposes and may not be modified. All use must give me credit as the original author.
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.
