Hyaluronan and RHAMM in Wound Repair and the “Cancerization” of Stromal Tissues

Figure 1

Schematic summarizing wound and tumor microenvironment remodeling in skin. The normal tissue architecture of skin is well-organized in both the epidermis, which consists of differentiated cohesive keratinocytes, and the dermis, which is composed of fibroblasts, blood vessels, and well-organized collagen fibrils amongst other ECM components. Tissue injury results in temporary changes in tissue architecture as keratinocytes dedifferentiate and migrate across wound gaps, proinflammatory macrophages migrate into the dermis, angiogenesis is promoted, and subpopulations of fibroblasts differentiate into myofibroblasts that organize collagen fibrils, which contribute to scar tissue. Tumor initiation also results in dedifferentiation, proliferation and migration/invasion of keratinocytes, influx of macrophages, differentiation of fibroblasts into myofibroblasts that increase deposition and scar like organization of collagen fibrils, and formation of new immature blood vessels. However, this disorganized tissue architecture is not transient as it is in wound repair but increases with tumor progression.