ADAPTATION OF EHRLICH ASCITES-CARCINOMA CELLS TO ENERGY DEPRIVATION IN-VIVO CAN BE ASSOCIATED WITH HEAT-SHOCK PROTEIN ACCUMULATION

Tumor adaptation to chronic energy starvation in vivo was studied on E hrlich ascites carcinoma (EAC) cells. EAC cells were isolated from mic e and incubated in a glucose-free medium containing blocators of mitoc hondrial ATP generation (rotenone, 2,4-dinitrophenol, or oligomycin). ATP level in the treated cells decreased to 3-4% oi the initial during 30 min of the incubation. The aggregation of cytoskeletal proteins, b lebbing, and necrotic death within 2-3 h were observed in ATP-depleted EAC which were isolated and treated in the exponential phase of growt h (5 days after inoculation), whereas stationary EAC (8 days after ino culation) were considerably more resistant to ATP depletion, and actin aggregation as well as bleb formation were suppressed in these cells despite the ATP loss. In contrast to the exponentially growing cells, thermotolerance and unexpected expression of inducible HSP68 and HSP27 as well as an elevated level of HSP90 were found in stationary EAC. S ince the stationary cells had decreased content of ATP, ATP/ADP ratio, and energy charge, we suggest that this energy dysbalance may be cond ucive to HSP induction within the ascites tumor in vivo, and, at the s ame time, EAC cells with elevated content of HSPs acquire resistance t o chronic energy starvation occurring in late stages of the tumor grow th. (C) 1995 Wiley-Liss, Inc.