Summary Hyperthermia and photoactivated hematoporphyrin derivative induce a dose-dependent reduction in the expression of the p250 surface melanoma-associated antigen on the human FME cell line. Expression of this glycoprotein antigen was quantitated by immunofluorescence flow cytometry based on the monoclonal antibody 9.2.27. Decrease in antigen expression was followed by a transient increase above the level for untreated cells, before normalization occurred about one week after treatment.These treatment-induced changes in antigen expression could partly be explained by changes in protein synthesis. This conclusion was based on the following observations: Hyperthermia and photoactivated hematoporphyrin derivative both inhibited protein synthesis. The latter increased again rapidly to rates above normal until antigen expression reached normal level, whereupon the protein synthesis rate decreased to normal.Inhibition of protein synthesis by cycloheximide 1 day after heating, prevented the recovery of antigen expression, demonstrating that protein synthesis is necessary for resumption of normal antigen expression.The changes in both antigen expression and protein synthesis were dose-dependent, and the magnitude and duration of the changes increased with increasing dose. The time courses of the changes in protein synthesis after two different treatments which both inactivated two logs of cells were almost identical, as were the time courses after two lower heat doses inactivating one log of cells. These similarities were reflected in the changes in antigen expression.At the same time as protein synthesis reached its maximum and antigen expression resumed normal level, an increase in the Golgi apparatus was observed ultrastructurally, indicating an increased synthesis rate and transportation of glycoproteins to the cell surface.
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.
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