Selection with melphalan or paclitaxel (Taxol) yields variants with different patterns of multidrug resistance, integrin expression and in vitro invasiveness

A melphalan-resistant variant (Roswell Park Memorial Institute (RPMI)-2650M 1) and a paclitaxel-resistant variant (RPMI-1650Tx) of the drug-sensitive h uman nasal carcinoma cell line, RPMI-2650. were established. The multidrug resistance (MDR) phenotype in the RPMI-2650Tx appeared to be P-glycoprotein (PgP)-mediated. Overexpression of multidrug resistant protein (MRP) family members was observed in the RPMI-2650M1 cells, which were also much more i nvasive in vitro than the parental cell line or the paclitaxel-resistant va riant. Increased expression of alpha (2), alpha (5), alpha (6), beta (1) an d beta (4) integrin subunits, decreased expression of alpha (4) integrin su bunit, stronger adhesion to collagen type IV, laminin, fibronectin and matr igel, increased expression of MMP-2 and MMP-9 and significant motility comp ared with the parental cells were observed, along with a high invasiveness in the RPMI-7650M1 cells. Decreased expression of the alpha (2) integrin su bunit, decreased attachment to collagen type IV, absence of cytokeratin 18 expression, no detectable expression of gelatin-degrading proteases and poo r motility may be associated with the non-invasiveness of the RPMI-2650Tx v ariant. These results suggest that melphalan exposure can result in not onl y a MDR phenotype. but could also make cancer cells more invasive, whereas paclitaxel exposure resulted in MDR without increasing the in vitro invasiv eness in the RPMI-2650 cells. (C) 2001 Elsevier Science Ltd. All rights res erved.