Abstract
The supernatant of a cell line of squamous cell carcinoma of the head and neck (SCCHN), PCI-50, was previously shown to induce activation, promote proliferation and increase antitumor cytotoxicity of freshly purified human natural killer (NK) cells and CD4+ T lymphocytes [Arch Otolaryngol Head Neck Surg (1994) in press]. This supernatant was found also to promote the growth of a variety of hematopoietic cell lines, including Jurkat, THP-1, K562, NK-92 or Epstein-Barr-virus-transformed B cell lines. The Jurkat cell line was selected as a reporter cell in an 18-h proliferation assay established to measure the growth-promoting activity of PCI-50 supernatant. The presence of soluble tumor-derived factors able to induce proliferation of Jurkat cells was demonstrated in the supernatant produced by several other SCCHN cell lines but not in that produced by a gastric cancer cell line (HR) or renal cell carcinoma line (5117G8). The growth-promoting PCI-50 supernatant was shown to contain 28±0.5 pg/ml interleukin-6, (IL-6) in vitro but was negative for interferon γ, IL-1, IL-2, IL-4, tumor necrosis factor α, granulocyte/macrophage-colony-stimulating factor and IL-12. The addition of any of these recombinant cytokines to Jurkat cell cultures did not significantly promote growth, while PCI-50 supernatant was consistently growth-stimulatory. This supernatant neither enhanced intracellular Ca2+ concentration in Jurkat cells nor induced up-regulation of activation antigens on the cell surface, although it supported growth of Jurkat cells in the absence of IL-2. The growth-promoting activity in the PCI-50 supernatant was acid-labile at pH 2 for 4 h, heat-resistant at 96 °C for 1 h and sensitive to treatments with trypsin and pepsin. Preincubation of the PCI-50 producer cells with tunicamycin or cyclohexamide reduced the level of growth-promoting activity in the supernatant. A partial purification of this activity was achieved using Amicon filtration, chromatography on concanavalin-A-Sepharose and then a hydroxyapatite column and high-pressure liquid chromatography gel filtration. The partially purified glycoprotein had a molecular mass of 50–70 kDa, as detemined by gel filtration.
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References
Cavanaugh PG, Nicolson GL (1990) Purification and characterization of aM r approximately 66,000 lung-derived (paracrine) growth factor that preferentially stimulates the in vitro proliferation of lung-metastasizing tumor cells. J Cell Biochem 43: 127
Cavanaugh PG, Nicolson GL (1991) Lung-derived growth factor that stimulates the growth of lung-metastasizing tumor cells: identification as transferrin. J Cell Biochem 47: 261
Friberg D, Bryant J, Shannon W, Whiteside TL (1994) In vitro cytokine production by normal human peripheral blood mononuclear cells to measure their immunocompetence and state of activation. Clin Diagn Lab Immunol 1: 261
Gillis S, Watson J (1980) Biochemical and biological characterization of lymphocyte regulatory molecules. V. Identification of an interleukin 2-producing human leukemia T cell line. J Exp Med 152: 1709
Heo DS, Snyderman CH, Gollin SM, Pan S, Walker E, Deka R, Barnes EL, Johnson JT, Herberman RB, Whiteside TL (1989) Biology, cytogenetics, and sensitivity of immunological effector cells of new head and neck squamous cell carcinoma lines. Cancer Res 49: 5167
Heo DS, Park J-G, Hata K, Day R, Herberman RB, Whiteside TL (1990) Evaluation of tetrazolium-based semi-automatic colorimetric assay for measurement of antitumor cytotoxicity. Cancer Res 50: 3681
Hirabayashi H, Yasumura S, Lin W-c, Amoscato A, Johnson JT, Herberman RB, Whiteside TL (1994) Production by human squamous cell carcinomas of a factor inducing activation and proliferation of immune cells. Arch Otolaryngol Head Neck Surg (in press)
Johnson JT, Rabin BS, Wagner RL (1987) Prostaglandin E2 of the upper aerodigestive tract. Ann Otol Rhinol Laryngol 96: 213
Klingemann H-G, Maki G, Gong J-H (1994) Characterization of a human cell line (NK-92) with phenotypical and functional characteristics of activated natural killer cells. Leukemia (in press)
Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227: 680
Lapointe H, Lampe H, Banerjee D (1992) Head and neck squamous cell line-induced suppression of in vitro lymphocyte proliferation responses. Arch Otolaryngol Head Neck Surg 106: 149
Luger TA, Stadler BM, Luger BM, Sztein M, Schmidt JA, Hawley-Nelson P, Grabner G, Oppenheim JJ (1983) Characteristic of an epidermal cell thymocyte-activating factor (ETAF) by human epidermal cells and a human squamous cell carcinoma cell line. J Invest Dermatol 81: 187
Luger TA, Uchida A, Kock A, Colot M, Micksche M (1985) Human epidermal cell and squamous carcinoma cells synthesize a cytokine that augments natural killer cell activity. J Immunol 134: 2477
Luger TA, Charon JA, Colot M, Micksche M, Oppenheim JJ (1983) Chemotatic properties of partially purified human epidermal cell-derived thymocyte-activating factor (ETAF) for polymorphonuclear and mononuclear cells. J Immunol 131: 816
Owen CS (1988) Quantitation of lymphocyte intracellular free calcium signals using Indo-1. Cell Calcium 9: 141
Rabinowich H, Vitolo D, Altarac S, Herberman RB, Whiteside TL (1992) Role of cytokines in the adoptive immunotherapy of an experimental model of human head and neck cancer by human IL-2-activated natural killer cells. J Immunol 149: 340
Shimizu Y, Weidmann E, Iwatsuki S, Herberman RB, Whiteside TL (1991) Characterization of human autotumor-reactive T cell clones obtained from tumor-infiltrating lymphocytes in liver metastasis of gastric carcinoma. Cancer Res 51: 6153
Snyderman CH, Heo DS, Johnson JT, d'Amico F, Barnes L, Whiteside TL (1991) Functional and phenotypic analysis of lymphocytes isolated from tumors and lymph nodes of patients with head and neck cancer. Arch Otolaryngol Head Neck Surg 117: 899
Snyderman CH, Klapan I, Heo DS, Wagner R, Schwartz D, Johnson JT, Whiteside TL (1994) Decreased in vitro production of prostaglandin E2 by squamous cell carcinoma of the head and neck. Arch Otolaryngol Head Neck Surg (in press)
Takeuchi A, Hayashi H, Naito Y, Baba T, Tamatani T, Onozaki K (1993) Human myelomonocytic cell line THP-1 produces a novel growth-promoting factor with a wide target cell spectrum. Cancer Res 53: 1871
Tan IB, Drexhage HA, Mullink R, Hensen-Logmans S, DeHaan-Meulman M, Snow GB, Balm AJM (1987) Immunohistochemical detection of retroviral-p15E-related material in carcinomas of the head and neck. Arch Otolaryngol Head Neck Surg 96: 251
Thorley-Lawson DA, Chess L, Stromingeo JL (1977) Suppression of in vitro EBV infection: A new role for human T lymphocytes. J Exp Med 146: 495
Vitolo D, Kanbour A, Johnson JT, Herberman RB, Whiteside TL (1993) In situ hybridization for cytokine gene transcripts in the solid tumor microenvironment. Eur J Cancer 3: 371
Yasumura S, Hirabayashi H, Schwartz DR, Toso JF, Johnson JT, Herberman RB, Whiteside TL (1993) Human cytototic T-cell lines with restricted specificity for squamous cell carcinoma of the head and neck. Cancer Res 53: 1461
Yasumura S, Weidmann E, Hirabayashi H, Johnson JT, Herberman RB, Whiteside TL (1994) HLA restriction and T-cell receptor Vß gene expression of cytotoxic T lymphocytes reactive with human squamous cell carcinoma of the head and neck. Int J Cancer 57: 297
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This work was supported in part by the Pathology Education and Research Foundation and American Cancer Society grant IM-696 to TLW
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Yasumura, S., Amoscato, A., Hirabayashi, H. et al. Proliferation of hematopoietic cell lines induced by a soluble factor derived from human squamous cell carcinomas of the head and neck. Cancer Immunol Immunother 39, 407–415 (1994). https://doi.org/10.1007/BF01534429
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DOI: https://doi.org/10.1007/BF01534429