title: Interleukin 2 receptor expression and interleukin 2 localisation in human solid tumor cells in situ and in vitro: evidence for a direct role in the regulation of tumour cell proliferation.
abstract: Frozen sections of 52 human solid tumours (38 malignant and 14 benign) of varied histogenesis were immunohistochemically stained with well characterised 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 examined, there was conspicuous staining for IL-2 in the tumour cell nuclei/nucleoli and perinuclear cytoplasm. In the human solid tumour cell lines G361 (melanoma), A549 (lung), MCF-7 (breast) and WiDR (colorectal), 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 distribution was similar to that exhibited by the tumour cells in situ (i.e., a nuclear/nucleolar localisation). In G361 melanoma cells, this IL-2 staining was present in proliferating cells but disappeared as the cultures approached confluence. Addition of an IL-2R beta subunit blocking antibody to growing G361 cultures (grown in the absence of rIL-2) resulted in a significant reduction in cell numbers. We propose, therefore, that the presence of immunoreactive IL-2 and IL-2R expression is characteristic of human malignant cells and that IL-2 may play a role in the autocrine stimulation of proliferation of malignant cells, such as G361 melanoma cells.
authors.affiliation: Department of Surgery, University of Aberdeen, Foresterhill, UK.
authors.forename: D N
authors.initials: DN
authors.lastname: McMillan
authors.forename: N M
authors.initials: NM
authors.lastname: Kernohan
authors.forename: M E
authors.initials: ME
authors.lastname: Flett
authors.forename: S D
authors.initials: SD
authors.lastname: Heys
authors.forename: D J
authors.initials: DJ
authors.lastname: Deehan
authors.forename: H F
authors.initials: HF
authors.lastname: Sewell
authors.forename: F
authors.initials: F
authors.lastname: Walker
authors.forename: O
authors.initials: O
authors.lastname: Eremin
mesh_terms: D002455:Cell Division; D006801:Humans; D007150:Immunohistochemistry; D007376:Interleukin-2 / Q000096:biosynthesis*; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured
chemical_list: D007376:Interleukin-2; D015375:Receptors, Interleukin-2