137 O - Induction of a heat shock response protects tumour cells from monocyte mediated lysis

Abstract

Hypothesis The proliferation of tumour cells despite tumouricidal mediators being present could be due induction of a heat shock response, a universal cellular defense mechanism in host cells and possibly tumour cells. Protection may be mediated either by increasing intracellular levels or surface expression of heat shock proteins (HSP) Aim To assess the effect of heat shock induction on tumour cell protection against host effector cells. Methods The heat shock response was induced in SW707 colorectal cells by either sodium arsenite (SA, Q-320μM for 6hrs) or by hyperthermia, (42°C for 20min). Monocyte mediated cytotoxicity, flow cytometry to assess surface expression of HSP60 and HSP70 or western blots of whole cell lysates to assess total HSP60 and HSP70 were performed. Results Cytotoxicity showed a significant decrease in all treated groups (p < 0.002) when compared to the control value of 40.45±0.812%. There was also a significant decrease in all groups (P < 0.001) when compared to the 42°C value of 11.50±0.799%. No significant alteration in surface expression of either HSP60 or HSP70 was seen. In whole cell lysates HSP60 expression was unaltered in all groups but HSP70 expression was increased with SA 40–160μM and with heat treatment. Conclusion Heat shocking tumour cells significantly protects them from Mø-mediated tumour cell lysis. Since the flow cytometric data indicate that there is no concomitant increase in surface expression of HSP60 and HSP70 on the tumour cell when the cells are heat shocked, it can be inferred from the whole cell lysate data that induction of intracellular HSP70 levels are in part responsible for the protective effect on the tumour cells. The proliferation of tumour cells despite tumouricidal mediators being present could be due induction of a heat shock response, a universal cellular defense mechanism in host cells and possibly tumour cells. Protection may be mediated either by increasing intracellular levels or surface expression of heat shock proteins (HSP) To assess the effect of heat shock induction on tumour cell protection against host effector cells. The heat shock response was induced in SW707 colorectal cells by either sodium arsenite (SA, Q-320μM for 6hrs) or by hyperthermia, (42°C for 20min). Monocyte mediated cytotoxicity, flow cytometry to assess surface expression of HSP60 and HSP70 or western blots of whole cell lysates to assess total HSP60 and HSP70 were performed. Cytotoxicity showed a significant decrease in all treated groups (p < 0.002) when compared to the control value of 40.45±0.812%. There was also a significant decrease in all groups (P < 0.001) when compared to the 42°C value of 11.50±0.799%. No significant alteration in surface expression of either HSP60 or HSP70 was seen. In whole cell lysates HSP60 expression was unaltered in all groups but HSP70 expression was increased with SA 40–160μM and with heat treatment. Heat shocking tumour cells significantly protects them from Mø-mediated tumour cell lysis. Since the flow cytometric data indicate that there is no concomitant increase in surface expression of HSP60 and HSP70 on the tumour cell when the cells are heat shocked, it can be inferred from the whole cell lysate data that induction of intracellular HSP70 levels are in part responsible for the protective effect on the tumour cells.