Date of Award

12-2013

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Program

Biomedical Sciences

Track

Cell Biology and Biochemistry

Research Advisor

Lisa K. Jennings, Ph.D.

Committee

John V. Cox, Ph.D. Malinda E.C. Fitzgerald, Ph.D. Karen A. Hasty, Ph.D. Mitchell A. Watsky, Ph.D.

Keywords

Cancer Biology, CD9, Matrix Metalloproteinases, MMP-9, Tetraspanin, Vascular Biology

Abstract

Cancer and vascular disease are the two most predominant causes of mortality in the United States. Potential regulatory mechanisms for these two diseases have consumed research interests. Tetraspanins are cell surface proteins that organize the cell membrane. Cellular membrane organization is a prerequisite for cellular signaling to occur. Deregulation of cellular signaling often precedes the formation of cancer or vascular disease phenotypes. This insinuates the necessity to understand how tetraspanins contribute to membrane organization and subsequent downstream signaling. This work examines tetraspanin CD9 contributions in a model of cancer cell invasion and vascular cell contraction. The findings presented here demonstrate that CD9 expression promotes human fibrosarcoma cell invasion by upregulating matrixmetalloproteinase-9 expression. These effects were dependent upon an extracellular region of CD9 and involved the presence and activity of the epidermal growth factor receptor. In the vascular cell model, CD9 elicited the actin arrangement and contraction of human aortic smooth muscle cells in a RhoA dependent manner. Taken together these provide insight on how tetraspanins regulate diverse cellular phenotypes.

DOI

10.21007/etd.cghs.2013.0135

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