EXPRESSION OF HEAT-SHOCK PROTEINS IN HUMAN LUNG AND LUNG CANCERS

Heat shock proteins (HSP) are highly conserved molecules whose expression is induced in eukaryotic cells following a broad spectrum of environmental stresses. These proteins can also be expressed by virally transformed cells and cancer cells and are important targets for T lymphocytes. Little is known about the abundance and distribution of HSP in the normal lung, the effect of cigarette smoking on their expression, or their expression in human lung carcinomas. We have used monoclonal antibodies coupled with immunohistochemical and immunoelectrophoretic techniques to evaluate the distribution of four different HSP (HSP 90 kD, HSP 73 kD/constitutive, HSP 72 kD/inducible, and HSP 63 kD) in normal lung (n = 14) and lung cancers (n = 15). In lung tissue from nonsmokers (n = 7), bronchiolar epithelial cells were intensely positive for HSP 90 kD and HSP 72 kD/inducible and weakly reactive for HSP 63 kD. Most macrophages also expressed these HSP at low levels, but no other parenchymal or immune/inflammatory cells were positive. Cigarette smoking did not modify the distribution or the intensity of HSP in bronchiolar epithelial cells, and macrophages from smokers expressed similar or lower levels of these HSP. Tumor cells from 14 of 15 lung carcinomas expressed one or more of the HSP. Considerable heterogeneity in the expression of HSP by cells in a given tumor was observed, explained in part by differences in the differentiation of the cells. Detection of HSP by immunohistochemical and immunoelectrophoretic techniques gave similar results for HSP 72 kD/inducible and HSP 90 kD. Although all tumor specimens were negative for HSP 73 kD/constitutive by immunohistochemical techniques, this protein was detected in all cases by immunoelectrophoresis. The strong expression of HSP is a characteristic feature of a limited number of lung cell types. The mechanisms controlling the expression of HSP and the function of these molecules in bronchiolar epithelial cells and macrophages require further study.