Interleukin 2 receptor expression and interleukin 2 localisation in human solid tumour 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.

Interleukin-2 expression in human carcinoma cell lines and its role in cell cycle progression

“…More recently, IL-2 protein and mRNA were also found to be expressed in several human carcinomas in vitro and in vivo by us and others (Lin et al, 1995;McMillan et al, 1995). In addition to intracellular IL-2, cell surface-associated IL-2, presumably bound to IL-2R on tumor cells, was detected by immunostaining and ow cytometry on variable proportions of tumor cells in culture grown in the absence of exogenous IL-2 (Lin et al, 1995).…”

“…The IL-2R appears to be expressed not only on hematopoietic cells but also on a wide variety of non-hematopoietic cells, including normal and malignant cells of the epithelial origin (Saneto et al, 1986;Weidmann et al, 1992;Plaisance et al, 1992Plaisance et al, , 1993Artz et al, 1992;Alileche et al, 1993;Ciacci et al, 1993;Yasumura et al, 1994;Lin et al, 1995;McMillan et al, 1995). Functions of the IL-2R chains in nonhematopoietic cells are not fully understood.…”

“…Functions of the IL-2R chains in nonhematopoietic cells are not fully understood. Binding of exogenous recombinant IL-2 to the IL-2R complex on these cells has been variously reported to enhance, decrease or not a ect cell proliferation (Saneto et al, 1986;Weidmann et al, 1992;Yasumura et al, 1994;McMillan et al, 1995). In addition, exogenous IL-2 was shown to induce changes in expression of surface markers (ICAM-1, HLA class I, HLA-DR and CD44) known to be associated with tumor progression Plaisance et al, 1993).…”

“…For a long time, IL-2 was thought to act only on cells of lympho-hematopoietic origin (Waldmann, 1991). More recently, it was shown that non-hematopoietic cells are also capable of IL-2 production and secretion (Alileche et al, , 1994Lin et al, 1995;McMillan et al, 1995). Alileche and coworkers reported production and secretion of biologically active IL-2 in the human melanoma cell line M14 and in myo®broblasts from post-radiation ®brosis in breast cancer (Alileche et al, 1994).…”

“…Alileche and coworkers reported production and secretion of biologically active IL-2 in the human melanoma cell line M14 and in myo®broblasts from post-radiation ®brosis in breast cancer (Alileche et al, 1994). McMillan and colleagues showed the presence of immunoreactive IL-2 in situ in a variety of human tumors as well as in tumor cell lines derived from these tumors (McMillan et al, 1995). We have recently reported that human carcinoma cell lines not only express IL-2R but contain mRNA for IL-2 and express IL-2 protein in the cytoplasm and on the cell surface (Lin et al, 1995).…”