Receptors for interleukin 2 on human squamous cell carcinoma cell lines and tumor in situ.
Several human head and neck squamous carcinoma cell lines were found to bind 125I-labeled or fluorescein-labeled interleukin 2 (IL-2). This binding was inhibited by an excess of cold ligand, IL-2, and by anti-p55 and anti-p70 monoclonal antibodies to the alpha and beta chains, respectively, of the IL-2 receptor (IL-2R). A small number (300/cell) of high-affinity IL-2R (2 x 10(-12) M) and a larger number (> 13,000/cells) of intermediate-affinity IL-2R (3 x 10(-10) M) were present on these tumor cells. By affinity cross-linking, tumor cells were shown to bind 125I-IL-2 to a M(r) 66,000 and 55,000 doublet peptide. The alpha and beta chains of the IL-2R also were detected on the surface of cultured tumor cells using the relevant monoclonal antibodies and flow cytometry. Immunoperoxidase staining with anti-p70 monoclonal antibody confirmed the expression of IL-2R on squamous cell carcinomas of the head and neck in situ. The presence of transcripts for p55/IL-2R-alpha and p70/IL-2R-beta in PCI-1 cells was confirmed by the polymerase chain reaction followed by hybridization to the IL-2R-alpha complementary DNA probe or IL-2R-beta complementary DNA probe, respectively. Our observations demonstrate that intermediate-affinity and high-affinity IL-2Rs are expressed on some human squamous cell carcinomas of the head and neck and that the receptors are functional, because growth of these tumor cell lines can be directly inhibited by exogenously supplied IL-2. The presence of IL-2R on human solid tumors could be important to consider, in addition to immunomodulatory effects of IL-2, in developing optimal therapeutic strategies for the administration of IL-2 to patients with cancer.
Weidmann
E
E
Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pennsylvania 15213.
Sacchi
M
M
Plaisance
S
S
Heo
D S
DS
Yasumura
S
S
Lin
W C
WC
Johnson
J T
JT
Herberman
R B
RB
Azzarone
B
B
Whiteside
T L
TL
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001483:Base Sequence; D001667:Binding, Competitive; D002294:Carcinoma, Squamous Cell / Q000737:chemistry* / Q000378:metabolism / Q000628:therapy; D005434:Flow Cytometry; D006258:Head and Neck Neoplasms / Q000737:chemistry* / Q000378:metabolism / Q000628:therapy; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D015603:Keratinocytes / Q000737:chemistry; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D015375:Receptors, Interleukin-2 / Q000032:analysis* / Q000276:immunology / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2