Age-related changes in the microenvironment are hypothesized to impact tumorigenesis. Osteopontin (green) is expressed in stromal fibroblasts coincident with the cell cycle inhibitor p21 (red) and p16 (data not shown) in a preneoplastic actinic keratosis skin lesion. Because osteopontin stimulates preneoplastic cell growth in vitro and in xenografts, this finding suggests that stromal-derived osteopontin plays a role in human cancer. For further details, please see Luo and coworkers on page 1018 in this issue.