Heat shock-induced shedding of cell surface integrins in A549 human lung tumor cells in culture

The human lung carcinoma-derived cell line A549 attaches to plastic and vitronectin-coated substrates in a manner dependent upon the specific cell surface integrin α(v)β₃. Exposure to hyperthermic temperatures (42-45°C) causes these cells to detach from the substrates. In heat-shocked cultures, the α(v), α₅, and β₃ integrin subunits remain attached to the substrate. Analysis of individual cells by fluorescence-activated cell sorting shows that cell surface levels of α(v)β₃ decrease by up to 10-fold in response to heat shock, while the abundance of another integrin found on the surface of A549 cells, α₃β₁, is only minimally affected by this stress. Heat shock-induced decreases in α(v)β₃ also occur in cells growing in suspension cultures, showing that physical attachment onto an extracellular substrate is not required for the hyperthermia-induced loss of this integrin. The heat shock-induced detachment of the cells and the shedding of α(v)β₃ from the cell surface can be inhibited by fetal bovine serum and α₂ macroglobulin. Reattachment of A549 cells to substrate is reduced by heat shock. These results demonstrate that heat shock can reduce the cell surface abundance of specific integrin subunits, some of which are involved at sites of cellular attachment to extracellular substrates. These findings may be relevant to the heterogeneous patterns of invasion and metastasis of human tumors following fevers or hyperthermia therapy.