Cellular migration is an integral component of normal physiological processes including embryogenesis, angiogenesis, and wound healing. Aberrations in existing mechanisms which dictate epithelial migration can lead to pathological conditions such as tumor metastasis. Receptor tyrosine kinases regulate a many of the cellular events necessary in the development of a migratory phenotype including cell junction dissolution, cell locomotion and matrix remodeling; however, the functional consequences of receptor tyrosine kinase activation display receptor type and cell type specificity. The work described in this thesis addresses selectivity of receptor tyrosine action at several crucial stages required for cell motility and invasion. My research supports a role for selective induction of matrix metalloprotease (MMP)-9 by motogenic receptor tyrosine kinases, and demonstrates that activity of this protease is required during the course of keratinocyte migration, in addition, these studies suggest that duration of MAPK activation is a basis of discrimination between the motogenic and non-motogenic actions of various receptor tyrosine kinases. In this manner, prolonged activation of signaling components provides a mechanism to modulate gene products, such as MMP-9, required during migration, and thus represents an underlying biochemical mechanism for receptor tyrosine kinase specificity in the generation of a migratory phenotype.

By detailing experimental and basic research, from premalignancy to fully invasive tumors, this book has wide applicability to all human carcinomas. No other group of human cancers is better positioned for the application of recently developed novel and targeted therapies, and this book uniquely presents the unusual opportunities tumors of the head and neck provide for clinical, translational, and basic science research. Cutting-edge and experimental treatment approaches are presented, along with future strategies and an evaluation of emerging technologies. - Presents a multi-disciplinary perspective from authorities in diverse fields - Addresses state-of-the art approaches in cancer research as well as other scientific opportunities in this field - Provides comprehensive yet easily comprehendible source of information

Written by internationally recognized leaders in Heparanase biology, the book’s eight chapters offer an opportunity for scientists, clinicians and advanced students in cell biology, tumor biology and oncology to obtain a comprehensive understanding of Heparanase’s multifaceted activities in cancer, inflammation, diabetes and other diseases, as well as its related clinical applications. Proteases and their involvement in cancer progression have been well addressed and documented; however, the emerging premise presented within this book is that Heparanase is a master regulator of aggressive cancer phenotypes and crosstalk with the tumor microenvironment. This endoglycosidase contributes to tumor-mediated remodeling of the extracellular matrix and cell surfaces, augmenting the bioavailability of pro-tumorigenic and pro-inflammatory growth factors and cytokines that are bound to Heparan sulfate. Compelling evidence ties Heparanase with all steps of tumor progression including tumor initiation, growth, angiogenesis, metastasis, and chemoresistance, supporting the notion that Heparanase is an important contributor to the poor outcome of cancer patients and a validated target for therapy. Unlike Heparanase, heparanase-2, a close homolog of Heparanase, lacks enzymatic activity, inhibits Heparanase, and regulates selected genes that promote normal differentiation and tumor suppression. Written by internationally recognized leaders in Heparanase biology, this volume presents a comprehensive understanding of Heparanase’s multifaceted activities in cancer, inflammation, diabetes and other diseases, as well as its related clinical applications to scientists, clinicians and advanced students in cell biology, tumor biology and oncology.