Changes in lipid and protein constituents of rafts and caveolae in multidrug resistant cancer cells and their functional consequences

The carcinogenic process Involves a complex series of genetic and biochemic al changes that enables transformed cells to proliferate, migrate to second ary sites and, in some cases, acquire mechanisms that make cancer cells res istant to chemotherapy. This phenomenon in its most common form is known as multidrug resistance (MDR). It is usually mediated by overexpression of P- glycoprotein (P-gp) or other plasma membrane ATPases that export cytotoxic drugs used in chemotherapy, thereby reducing their efficacy. However, addit ional adaptive changes are likely to be required in order to confer a full MDR phenotype. Recent studies have shown that acquisition of MDR is accompa nied by upregulation of lipids and proteins that constitute lipid rafts and caveolar membranes, notably glucosylceramide and caveolin. These changes m ay be related to the fact that in MDR cells a significant fraction of cellu lar P-gp is associated with caveolin-rich membrane domains, they may be inv olved in drug transport and they could have an impact on drug-induced apopt osis and on the phenotypic transformation of MDR cancer cells.