Hyluronan (HA), a nonsulfated high-molecular mass glycoaminoglycan, has been assigned as a clinical marker for the progression of various tumors. We found that RA stimulation of QG90, a cell line derived from human small-cell lung carcinoma, activates the secretion of matrix metalloproteinase-2 (MMP-2) in a focal adhesion kinase (FAK)-dependent manner. HA stimulation of QG90 cells activated MMP-2 secretion in a time-dependent manner. Larger sizes of HA seemed to have higher activities than smaller size one in MMP-2 secretion. Under RA stimulation, tyrosine phosphorylation of cellular proteins including FAK was activated. By use of antisense oligonucleotide to FAK, we found that FAK signaling was required for the activation of MMP-2 secretion and for the sustained activation of ALAP kinase by HA treatment. These results strongly suggest that FAK-MAPK signaling is involved, at least in part, in RA-dependent activation of MMP-2 secretion in QG90 cells. (C) 2002 Elsevier Science (USA).