Chronic inflammation plays important roles at different stages of cancer development, including carcinogenesis, tumor invasion, and metastasis. In this study, expression of angiopoietin-like protein 2 (Angptl2), recently identified as a chronic inflammation mediator in skin tissues, is highly correlated with the frequency of carcinogenesis in a chemically induced skin squamous cell carcinoma (SCC) mouse model. Furthermore, expression of Angptl2 in tumor cells promotes not only tumor angiogenesis and lymphangiogenesis, but also the acquisition of mesenchymal invasive characteristics in tumor cells through activation of TGF-b/Smad signaling, resulting in worse outcomes. This image represents a significantly increased tumor angiogenesis in SCC of Angptl2 transgenic (K14-Angptl2) mice. For details, see the article by Aoi and colleagues on page 7502 of this issue.