INTERLEUKIN-2 RECEPTOR EXPRESSION AND INTERLEUKIN-2 LOCALIZATION IN HUMAN SOLID TUMOR-CELLS IN-SITU AND IN-VITRO - EVIDENCE FOR A DIRECT ROLE IN THE REGULATION OF TUMOR-CELL PROLIFERATION

Frozen sections of 52 human solid tumours (38 malignant and 14 benign) of varied histogenesis were immunohistochemically stained with well c haracterised monoclonal antibodies (MAbs) to human interleukin 2 (IL-2 ) and the alpha and beta chains of its receptor (R). In all malignant specimens, the tumour cells expressed the IL-2R beta subunit (p75) but not the IL-2R alpha subunit (CD25). In 36 of 38 malignant tumours exa mined, there was conspicuous staining for IL-2 in the tumour cell nucl ei/nucleoli and perinuclear cytoplasm. In the human solid tumour cell lines G361 (melanoma), A549 (lung), MCF-7 (breast) and WiDR (colorecta l), both subunits of the IL-2R appeared to be expressed, although the alpha subunit only weakly. Exogenous addition of human recombinant (r) interleukin 2 altered cell numbers in 3 of the 4 cell lines (WiDR was refractory). When grown in the absence of exogenously added rIL-2, IL -2 staining was observed in all cell lines. The pattern of distributio n was similar to that exhibited by the tumour cells in site (i.e., a n uclear/nucleolar localisation). In G361 melanoma cells, this IL-2 stai ning was present in proliferating cells but disappeared as the culture s approached confluence. Addition of an IL-2R beta subunit blocking an tibody to growing G361 cultures (grown in the absence of rIL-2) result ed in a significant reduction in cell numbers. We propose, therefore, that the presence of immunoreactive IL-2 and IL-2R expression is chara cteristic of human malignant cells and that IL-2 may play a role in th e autocrine stimulation of proliferation of malignant cells, such as G 361 melanoma cells. (C) 1995 Wiley-Liss, Inc.