Hyaluronan production increases the malignant properties of mesothelioma cells

Malignant pleural mesotheliomas is in most cases associated with elevated a mounts of hyaluronan. To investigate the importance of hyaluronan for the m alignant properties of mesotheliomas, we have expressed murine hyaluronan s ynthase 2 (HAS2) in the non-hyaluronan producing mesothelioma cell line, Me ro-25. We found that upon hyaluronan overproduction the mesothelioma cells changed their epitheloid character to a fibroblastic phenotype and were sur rounded by pericellular matrices, the size of which correlated to the amoun t of synthesized hyaluronan. HAS2-transfected cells with the ability to syn thesize about 520 ng hyaluronan/5 x 10(4) cells/24 h exhibited about a 2-fo ld increase in the expression of the cell surface hyaluronan receptor CD44 and their locomotion increased compared to that of mock-transfected Mero-25 cells. Furthermore, the malignant properties of mesothelioma cell clones a s determined by the ability to grow in a soft agar assay correlated to thei r hyaluronan production. These results provide evidence for an important ro le of hyaluronan in the aggressive spread of mesotheliomas in adjacent non- cancerous stromal tissues. (C) 2001 Cancer Research Campaign http://www.bjc ancer.com.