Differential growth regulation in human melanoma cell lines by TIMP-1 and TIMP-2

We investigated the role of tissue inhibitor of :metalloproteinase (TIMP)-1 and TIMP-2 in the growth regulation. Primary (PM-WK and KHm-4), recurrent primary (RPM-EP and RPM-MC), lymph node metastatic (MM-AN, MM-BP and MM-RU) , and a visceral metastatic (MM-LH) melanoma cell lines were used. Reverse transcriptase-coupled polymerase chain reaction and Western blotting reveal ed that all expressed and produced TIMP-1 and TIMP-2 except for PM-WK, whic h neither expressed nor produced TIMP-1. TIMP-1 and TIMP-2 secretion levels were measured by enzyme-linked immunosorbent assay in supernatants of cell s. We found that the TIMP-1 production level was correlated with the cell m igration rate. Moreover, TIMP-1 enhanced the cell migration of PM-WK. The g rowth of the primary melanoma cell lines was stimulated by TIMP-1 and inhib ited by TIMP-2. In contrast, the growth of the visceral metastatic melanoma cell line was stimulated by TIMP-2. (C) 2001 Academic Press.