Changes in antigen expression on human FME melanoma cells after exposure to hypoxia and acidic pH, alone or in combination

Quantitative changes in the expression of two tumour-associated surface antigens on human FME melanoma cells were studied by flow cytometry after exposure to hypoxia and acidic pH, either alone or in combination. The expression of the p250 antigen recognized by the monoclonal antibody (MAb) 9.2.27 was reduced immediately after exposure to hypoxia. The magnitude and duration of the reduction increased with increasing exposure time. Twelve to 16 hr after the end of a 6-hr exposure to hypoxia the antigen expression reached the normal level, followed by a temporary increase above this level. The p97a antigen recognized by the 4.1 MAb underwent similar changes after exposure to hypoxia for 6 hr. After exposure to hypoxia in acidic environment, the magnitude and duration of the reduction in the expression of the p250 antigen increased with increasing acidity. The enhancement in antigen expression above the normal level was less after hypoxia at acidic pH than after hypoxia at physiological pH. The combined treatment had an additive effect on the expression of the melanoma-associated antigen but did not enhance hypoxia-induced cell killing. The observed changes in antigen expression might be of importance if hypoxic tumour cells are subjected to MAbs conjugated to radioisotopes or cytotoxic agents for diagnostic or therapeutic purposes.