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This book provides potential novel targets for therapies of human cancer and inflammatory diseases. The studies in this book have revealed the cryptic activity within the FnIII-1 module modulates the tissue inflammatory response and suggests that fibronectin (Fn) matrix remodeling can induce the expression of cytokines by stromal cells present in the tissue microenvironment, providing evidence for a previously unrecognized link between fibronectin matrix remodeling and the regulation of the innate immune system. These studies have dissected FnIII-1c's effects on fibronectin matrix from its effects on the activation of intracellular signaling, elucidated the mechanism by which unfolding of fibronectin Type III-1 domain regulates inflammatory response in tissue microenvironment and clarified how local mechanical properties within tissue microenvironment may protect tumor cells from therapeutic treatment.