HSP27 AS A MEDIATOR OF CONFLUENCE-DEPENDENT RESISTANCE TO CELL-DEATH INDUCED BY ANTICANCER DRUGS

Resistance of colorectal cancer cells to chemotherapeutic drugs increa ses as cells reach confluence. Here we show that the small stress prot ein HSP27, which has been described to block necrotic and apoptotic ce ll death, accumulates in confluent human colorectal cancer cell lines HT-29 and Caco2. Cell confluence also induces HSP27 phosphorylation an d changes in its intracellular distribution. We also show that overexp ression of human HSP27 by transfection of HT-29 cells increased the re sistance of cells to doxorubicin or cisplatin and prevented drug-induc ed apoptosis. Interestingly, nonconfluent HSP27-transfected cells and confluent control cells in which HSP27 is expressed at the same level displayed a similar drug resistance. HSP27-transfected cells did not e xhibit an enhanced resistance when they reached confluence, nor was th ere an increased accumulation of HSP27. We have previously shown that HSP27 expression blocks tumor necrosis factor-induced cell death as a result of decreasing intracellular reactive oxygen species (ROS). Here we show that HSP27 overexpression in HT-29 cells, obtained either by transfection or by growing the cells at high density, correlated with a significant ROS decrease. We conclude that cell confluent-dependent HSP27 accumulation, probably due to its ability to decrease ROS levels , is essential for the establishment of the resistance of colorectal c ancer cells when reaching confluence.