To understand the role of retinoids in chemoprevention, the authors examined the effects of 13-cis retinoic acid (cRA) on squamous cell carcinoma proliferation and adhesion to extracellular matrix proteins. The antiproliferative effects of cRA were first seen on day 11 (66% inhibition) and progressed through day 19 (96% inhibition). Using an adhesion assay, the authors then investigated the effects of cRA and transforming growth factor-beta(1) (TGF-beta(1)) on cellular adhesion to purified type TV collagen, fibronectin, and laminin matrices. Cells treated for 4 days with TGF-beta(1) increased adhesion by 15% to 29%, and cells treated with cRA increased adhesion by 19% to 39%. However, the use of cRA alone resulted in a decrease in adhesion when tumor cells were treated for 7 days (20% to 32%) and 15 days (25% to 40%). The authors also discuss how cRA acts as a differentiating agent on squamous cell carcinoma.