Characterization of a novel cell line from pleomorphic adenoma of the parotid gland with myoepithelial phenotype and producing interleukin‐6 as an autocrine growth factor

A cell line was obtained from a primary culture of a pleomorphic adenoma of the parotid gland in a 24‐year‐old woman. The cells of the line (PA 16/23) grew spontaneously in minimal culture conditions and showed stable morphologic characteristics over 30 passages. PA 16/23 cells had immunophenotypic and ultrastructural features similar to those of transformed myoepithelial cells, which are regarded as the precursors of pleomorphic adenomas. Furthermore, these cells have been demonstrated immunocytochemically to contain interleukin‐6 (IL‐6) on light and electron microscopic examination. IL‐6 also has been found by enzyme‐linked immunosorbent assay in the culture supernatant and has been proven to be capable of stimulating growth of the PA 16/23 cells. Cancer 1992; 70:559–568.

[1]  K. Kato,et al.  Epstein-Barr virus-immortalized B cells produce IL-6 as an autocrine growth factor. , 1990, Immunology.

[2]  I. Dardick,et al.  Myoepithelial cells in salivary gland tumors. An immunohistochemical study. , 1985, Archives of pathology & laboratory medicine.

[3]  P. Higgins,et al.  Histogenesis of benign pleomorphic adenoma (mixed tumor) of the major salivary glands: An ultrastructural and immunohistochemical study , 1984, The American journal of surgical pathology.

[4]  R. Stead,et al.  An immunohistochemical study of pleomorphic adenomas of the salivary gland: glial fibrillary acidic protein-like immunoreactivity identifies a major myoepithelial component. , 1988, Human pathology.

[5]  S. Sumitomo,et al.  IMMUNOHISTOCHEMICAL STUDIES OF KERATIN DISTRIBUTION IN SALIVARY GLAND TUMORS , 1985 .

[6]  T. Nakajima,et al.  Normal and neoplastic myoepithelial cells in salivary glands: an immunohistochemical study. , 1987, Human pathology.

[7]  K. Shirasuna,et al.  A myoepithelial cell line established from a human pleomorphic adenoma arising in minor salivary gland , 1980, Cancer.

[8]  H Stein,et al.  Immunoenzymatic labeling of monoclonal antibodies using immune complexes of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP complexes). , 1984, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[9]  J. Batsakis,et al.  The pathology of head and neck tumors: the myoepithelial cell and its participation in salivary gland neoplasia, Part 17. , 1983, Head & neck surgery.

[10]  B. Gusterson,et al.  Immunocytochemical identification of cell types in pleomorphic adenoma, with particular reference to myoepithelial cells , 1985, The Journal of pathology.

[11]  H. Denk,et al.  Immunocytochemistry of intermediate filament proteins present in pleomorphic adenomas of the human parotid gland: characterization of different cell types in the same tumor. , 1982, Differentiation; research in biological diversity.

[12]  S. Akira,et al.  Biological and clinical aspects of interleukin 6. , 1990, Immunology today.

[13]  Kierszenbaum Al.  The ultrastructure of human mixed salivary tumors. , 1968 .

[14]  T. Ogihara,et al.  Interleukin-6 stimulates c-myc expression and proliferation of cultured vascular smooth muscle cells. , 1990, Biochemistry international.

[15]  P. Wilson,et al.  Immunohistochemical localisation of keratin and luminal epithelial antigen in myoepithelial and luminal epithelial cells of human mammary and salivary gland tumours. , 1982, Pathology, research and practice.

[16]  G. Tosato,et al.  Identification of interleukin-6 as an autocrine growth factor for Epstein-Barr virus-immortalized B cells , 1990, Journal of virology.

[17]  W. D. Ball,et al.  Differentiation of myoepithelial cells in the developing rat sublingual gland. , 1979, The American journal of anatomy.

[18]  M. Brandi,et al.  Insulin stimulates cell growth of a new strain of differentiated rat thyroid cells , 1987, Molecular and Cellular Endocrinology.

[19]  J. Renauld,et al.  Materials and Methods Briefdefinitive Report , 2022 .

[20]  T. Hirano,et al.  Structure and expression of human B cell stimulatory factor‐2 (BSF‐2/IL‐6) gene. , 1987, The EMBO journal.

[21]  Y. Yaku.  Ultrastructural studies on the development of human fetal salivary glands. , 1983, Archivum histologicum Japonicum = Nihon soshikigaku kiroku.

[22]  P. Sehgal,et al.  Monocyte-derived human B-cell growth factor identified as interferon-beta 2 (BSF-2, IL-6). , 1988, Science.

[23]  A. Muraguchi,et al.  Involvement of IL-6 in mesangial proliferative glomerulonephritis. , 1989, Journal of immunology.

[24]  U. Santhanam,et al.  Cytokine-induced production of IFN-beta 2/IL-6 by freshly explanted human endometrial stromal cells. Modulation by estradiol-17 beta. , 1989, Journal of immunology.

[25]  Rachel Jenkins,et al.  Immunohistochemical demonstration of S‐100 protein in salivary gland neoplasms , 1985, The Journal of pathology.

[26]  I. Dardick,et al.  Pleomorphic adenoma, I: Ultrastructural organization of "epithelial" regions. , 1983, Human pathology.

[27]  M. Mori,et al.  Various expressions of modified myoepithelial cells in salivary pleomorphic adenoma. Immunohistochemical studies. , 1987, Pathology, research and practice.

[28]  H. Yagisawa,et al.  IL1 induces proliferation and IL6 mRNA expression in a human astrocytoma cell line: positive and negative modulation by chorela toxin and cAMP. , 1990, Biochemical and biophysical research communications.

[29]  C. Ph,et al.  An ultrastructural study of cartilaginous zones and surrounding epithelium in mixed tumors of salivary glands and skin. , 1981 .

[30]  J. Banchereau,et al.  IL-4 is an essential factor for the IgE synthesis induced in vitro by human T cell clones and their supernatants. , 1988, Journal of immunology.

[31]  K. Weber,et al.  The expression of different intermediate-sized filaments in human salivary glands and their tumours. , 1982, Pathology, research and practice.

[32]  T. Saku,et al.  A Comparative Study On the Immunolocalization of Keratin and Myosin in Salivary Gland Tumors , 1984, Acta pathologica japonica.

[33]  H Stein,et al.  Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. , 1984, Journal of immunology.

[34]  H. Yoshida,et al.  Intermediate-sized filaments and specific markers in a human salivary gland adenocarcinoma cell line and its nude mouse tumors. , 1985, Cancer research.

[35]  R. Lam,et al.  An electron microscopic histochemical study of the histogenesis of major salivary gland pleomorphic adenoma. , 1985, Ultrastructural pathology.

[36]  Johannes Gerdes,et al.  Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation , 1983, International journal of cancer.

[37]  A. Zilberstein,et al.  Growth inhibition of human breast carcinoma and leukemia/lymphoma cell lines by recombinant interferon-beta 2. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[38]  P. Sehgal,et al.  Interleukin-6 immunoreactivity in human tumors. , 1989, The American journal of pathology.

[39]  H. Asaoku,et al.  Autocrine generation and requirement of BSF-2/IL-6 for human multiple myelomas , 1988, Nature.

[40]  P. Sehgal,et al.  Induction of β 2-interferon by tumor necrosis factor: A homeostatic mechanism in the control of cell proliferation , 1986, Cell.

[41]  C. Uyttenhove,et al.  Interleukin-HP1, a T cell-derived hybridoma growth factor that supports the in vitro growth of murine plasmacytomas , 1987, The Journal of experimental medicine.

[42]  J. Polak,et al.  Immunogold staining procedure for the localisation of regulatory peptides , 1982, Peptides.

[43]  L. Leduy,et al.  Interleukin-6 and its receptor are expressed in human intestinal epithelial cells , 1989, Virchows Archiv. B, Cell pathology including molecular pathology.

[44]  J. Ghrayeb,et al.  Synthesis and secretion of multiple forms of beta 2-interferon/B-cell differentiation factor 2/hepatocyte-stimulating factor by human fibroblasts and monocytes. , 1988, The Journal of biological chemistry.

[45]  S. Shimizu,et al.  Establishment of two interleukin 6 (B cell stimulatory factor 2/interferon beta 2)-dependent human bone marrow-derived myeloma cell lines , 1989, The Journal of experimental medicine.

[46]  J. Szostak.  Enzymatic activity of the conserved core of a group I self-splicing intron , 1986, Nature.

[47]  T. W. Keenan,et al.  Intermediate-sized filaments of the prekeratin type in myoepithelial cells , 1980, The Journal of cell biology.

[48]  A. Mantovani,et al.  IL-1 stimulates IL-6 production in endothelial cells. , 1989, Journal of immunology.

[49]  M. Jourdan,et al.  Paracrine rather than autocrine regulation of myeloma-cell growth and differentiation by interleukin-6. , 1989, Blood.

[50]  T. Nakajima,et al.  An immunoperoxidase study of S-100 protein distribution in normal and neoplastic tissues , 1982, The American journal of surgical pathology.

[51]  I. Dardick,et al.  Myoepithelial cells in salivary gland tumors--revisited. , 1985, Head & neck surgery.

[52]  H. Yoshida,et al.  Generation of cells with phenotypes of both intercalated duct-type and myoepithelial cells in human parotid gland adenocarcinoma clonal cells grown in athymic nude mice , 1986, Virchows Archiv. B, Cell pathology including molecular pathology.

[53]  H. Karasuyama,et al.  Growth autonomy and tumorigenicity of interleukin 6-dependent B cells transfected with interleukin 6 cDNA , 1990, The Journal of experimental medicine.

[54]  R. Simpson,et al.  Identification of the human 26-kD protein, interferon beta 2 (IFN-beta 2), as a B cell hybridoma/plasmacytoma growth factor induced by interleukin 1 and tumor necrosis factor , 1987, The Journal of experimental medicine.

[55]  J. Langdon,et al.  Ultrastructural analysis of salivary gland pleomorphic adenoma, with particular reference to myoepithelial cells , 1985, Histopathology.

[56]  T. Hirano,et al.  Human B-cell differentiation factor defined by an anti-peptide antibody and its possible role in autoantibody production. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[57]  T. Luger,et al.  IFN-beta 2, B cell differentiation factor 2, or hybridoma growth factor (IL-6) is expressed and released by human epidermal cells and epidermoid carcinoma cell lines. , 1989, Journal of immunology.

[58]  G. Tosato,et al.  Interferon-beta 2/interleukin 6 is a co-stimulant for human T lymphocytes. , 1988, Journal of immunology.