• Characterization of Novel Extracellular Matrix (Ecm) Proteins (Mgp and Lumican) and Their Implications in Vascular Development, Angiogenesis, and Cancer

      Sharma, Bikram (2013-01-30)
      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.
    • Manipulation of Angiogenesis by Cyclosporine-A and Extracellular Matrix Molecules

      Pandey, Raghav (2012-10-19)
      Angiogenesis is the formation of new capillaries from pre-existing capillaries. Angiogenesis plays an important role in the blood vessel formation required during embryonic development, tissue injury, wound healing, and menstruation. It also plays a major role in tumor progression. We propose a mechanism that links the developmental pathways to a therapeutic pathway. Moreover, we show anti-angiogenic nature of an FDA approved immunosuppressant. Extra cellular matrix (ECM) has an important role in maintaining the shape and structure of organisms and in signaling mechanisms. Two major components of ECM are lumican and Magp2. Investigating their role might help us further link angiogenesis to tumor progression in cancer. We show the pro-angiogenic nature of Magp2 in an in-vivo model. Although this project is in early stages, it would provide a good foundation for future study. The aim of this thesis was to check the effect of blocking angiogenesis on tumor growth through different ECM proteins (Lumican and Magp2) and therapeutics (cyclosporine-A). Studying the progression of tumor links the chapters together.