Date of Award

2012

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biology

First Advisor

Ghosh, Swapan

Abstract

Extracellular matrix (ECM) constitutes a large component of our tissue structure. Primarily, ECM provides structural and adhesive support to our cells, but it also controls cellular signaling and behavior. Homeostasis of extracellular matrix composition and function is maintained by our body through a balanced synthesis, degradation and remodeling of ECM. However, under pathological conditions and genetic mutations, ECM homeostasis is disrupted due to deregulation in ECM synthesis, assembly, remodeling, and degradation. A number of diseases, including cardiovascular diseases and cancer, are found to occur due to alterations in ECM. Therefore, targeting ECM can be an attractive therapeutic approach to treat these diseases, and it requires our complete understanding of the ECM molecules and the molecular mechanism it employs in controlling cellular functions. To this end, this study is aimed at the characterization of two ECM proteins—Matrix Gla Protein (MGP) and Lumican—for their roles in vascular development, angiogenesis, and cancer. Findings from this study show that MGP is a critical ECM regulator that promotes angiogenic resolution by suppressing endothelial sprouting and stabilizing vascular lumen formation. In addition, MGP also inhibits tumor growth by inhibiting tumor angiogenesis. On the other hand, our findings show Lumican suppresses tumor growth and has anti-angiogenic activity in a context specific manner.

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