Archives of Gynecology and Obstetrics

, Volume 258, Issue 1, pp 25–33 | Cite as

Interleukin-6 (IL-6) production in carcinoma of the cervix

  • H. Takanol
  • K. Harigaya
  • G. Ishii
  • Y. Sugaya
  • S. Soeta
  • T. Nunoyamal
  • H. Shirasawa
  • K. Shimizu
  • H. Tokita
  • B. Simizu
  • A. Mikata
  • S. Sekiya
Originals

Abstract

Interleukin-6 (IL-6) is a pleiotropic cytokine that is not only a mediator in major immunologic reactions but also a growth factor of keratinocytes. We studied the IL-6 secretion in vitro of 15 human cell lines derived from both squamous cell carcinoma (SCC) and adenocarcinoma of the uterine cervix. Four of the eight well differentiated SCC secreted a large amount (> 1500 pg/48 h/106 cells) of IL-6 in nude mice. In contrast, poorly differentiated SCC cell lines and all of the 7 adenocarcinoma cell lines secreted a small amount (< 500 pg/48 h/106 cells of IL-6). The expression of IL-6 mRNA of the cell lines correlated well with their IL-6 secretion potential. However, the expression of IL-6 receptor did not correlate with the IL-6 secretory potential. We also studied the IL-6 secretion of freshly isolated normal squamous epithelium and of dysplastic epithelium. In culture, two normal squamous epithelia secreted a large amount (> 2000 pg/48 h/106 cells), whereas 8 dysplasia epithelia secreted an extremely small amount (< 10 pg/48 h/106 cells). About one-third of patients with SCC had a raised serum IL-6 value. IL-6 production may help to differentiate between SCC and adenocarcinoma of the uterine cervix. IL-6 regulation seems to change in the course of SCC carcinogenesis.

Key words

Interleukin-6 (IL-6) Carcinoma of the uterine cervix Histologic type Carcinogenesis 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Adachi M, Yasunaga M, Nakayama K, Jikai J, Yamaguchi N, Ryo R (1991) Expression and detection of platelet specific genes in human megakaryocytic cells. Jpn J Clin Pathol 39:1308–1316 [in Japanese]Google Scholar
  2. 2.
    Akira S, Taga T, Kishimoto T (1993) Interleukin-6 in biology an medicine. Adv Immunol 54:1–78PubMedGoogle Scholar
  3. 3.
    Berek SJ, Chung C, Kaldi K, Watoson JM, Knox RM, Martinez-Maza O (1991) Serum interleukin-6 levels correlate with disease status in patients with epithelial ovarian cancer. Am J Obstet Gynecol 164:1038–1043PubMedGoogle Scholar
  4. 4.
    Brown AT (1991) Molecular biology Labfax. BIOS Scientific Publishers Limited, ManchesterGoogle Scholar
  5. 5.
    Eustace D, Han X, Gooding R, Rowbottom A, Riches L, Heyderman E (1993) Interleukin-6 (IL-6) functions as an autocrine growth factor in cervical carcinomas in vitro. Gynecol Oncol 50:15–19PubMedGoogle Scholar
  6. 6.
    Fushiki H (1992) Characterization of two novel cell lines established from a single human uterine cervical adenocarcinoma, and their chemosensitivites and hormonal effects on their proliferation. Acta Obst Gyneac Jpn 44:397–404 [in Japanese]Google Scholar
  7. 7.
    Harigaya K, Handa H (1985) Generation of functional clonal cell lines from human bone marrow stroma. Proc Natl Acad Sci USA 82:3477–3480PubMedGoogle Scholar
  8. 8.
    Hayakawa O, Kudo R, Koizumi M, Yamauchi O, Yamamoto H, Takehara M (1988)Establishment and characterization of cell line derived from human uterine cervical adenocarcinoma and its chemotherapy to anticancer drugs. The Sapporo Med J 57:603–611 [in Japanese]Google Scholar
  9. 9.
    Hirai Y, Kawaguchi T, Shibata H, Yudate T, Sakatani K, Toyama K, Hasumi K, Kitagawa T, Noda T (1993) Establishment of epithelial cell cultures derived from cervical exfoliated cells: characterization and transfection with HPV DNA. In: Hashimoto K (ed) Proceedings of the Jap Cancer Association. Jap Cancer Association, Tokyo, p 136Google Scholar
  10. 10.
    Hirano T, Taga T, Yasukawa K, Nakajima K, Nakano N, Takatsuki F, Shimizu M, Murashima A, Tsunasawa S, Sakiyama F, Kishimoto T (1987) Human B cell differentiation factor defined by a anti-peptide antibody and its possible role in auto-antibody production. Proc Natl Acad Sci USA 84:228–231PubMedGoogle Scholar
  11. 11.
    Ishiwata T, Nozawata S, Kiguchi K, Kurihara S, Okumura H (1978) Establishment of human uterine cervical cancer cell line and comparative studies between normal and malignant uterine cervical cells in vitro. Acta Obst Gynaec Jpn 30:731–738Google Scholar
  12. 12.
    Ishiwata I, Soma M, Ono I, Nakaguchi T, Nozawa S, Ishikawa H (1988) Establishment and characterization of uterine cervical glassy cell carcinoma cell line (HOKUG). Human cell 1:320–321 [in Japanese]Google Scholar
  13. 13.
    Jones HW Jr., McKusick VA, Harper PS, Wuu KD (1971) George Otto Gey (1899–1970) The HeLa cell and a reappraisal of its origin. Obstet Gynecol 38:945–949PubMedGoogle Scholar
  14. 14.
    Jones III HW (1988) Invasive cancer of the cervix. In: Jones III HW, C. Wa, Burnett LS (eds) Novak's textbook of gynecology, 1th edn. Williams & Wilkins, Baltimore, pp 679–715Google Scholar
  15. 15.
    Martin P, Papayannopoulo Th (1982) HEL cells: a new human erthroleukimia cell with spontaneous and induced globin expression. Science 216:1233–1235PubMedGoogle Scholar
  16. 16.
    Matsunaga K, Mashiba H, Gojobori M, Jimi S (1979) Antibody-dependent cell-mediated cytotoxicity of sera from cancer patients against cultured cervical cancer cell lines. Gann 70:1–7PubMedGoogle Scholar
  17. 17.
    Nunoyama T, Sekiya S, Takano H, Shirasawa H, Tokita H, Takamizawa H (1992) Establishment and characterization of YUMOTO cell line — HPV negative cell cultures derived from uterine cervical keratinizing squamous cell carcinoma cells. In: Toyoshima K (ed) Proceedings of the Jap Cancer Association, Jap Cancer Association, Tokyo, p 210Google Scholar
  18. 18.
    Pattillo RA, Hussa RO, Story MT, Ruckert ACF, Shalaby MA, Mattingly RF (1977) Tumor antigen and human chorionic gonadotropin in CaSki cells; a new epidermoid cervical cancer cell line. Science 196:1456–1458PubMedGoogle Scholar
  19. 19.
    Sekiya S, Tanaka N, Takamizawa H (1990) Production of various marker substances in human ovarian cell lines of epithelial origin. Arch Gynecol Obstet 248:103–110PubMedGoogle Scholar
  20. 20.
    Shirasawa H, Tomita Y, Kubota K, Kasai T, Sekiya S, Takamizawa H, Shimizu B (1986) Detection of human papillomavirus type 16 and evidence for integration into the cell DNA in cervical dysplasia. J Gen Virol 67:2011–2015PubMedGoogle Scholar
  21. 21.
    Suzumori K, Yasui M (1988) NUZ-1. Human Cell 1:454 [in Japanese]Google Scholar
  22. 22.
    Taguchi S (1981) Establishment and characterization of the human uterine cervical epidermoid cancer cell line. Acta Obstet Gynaec Jpn 33:1180–1188 [in Japanese]Google Scholar
  23. 23.
    Takenawa J, Kaneko Y, Fukumoto M, Fukatsu A, Hirano T, Fukuyama H, Nakayama H, Fujita J, Yoshida O (1991) Enhanced expression of interleukin-6, in primary human renal cell carcinomas. J Natl Cancer Inst 83:1688–1672Google Scholar
  24. 24.
    Tokita H, Tanaka N, Sekimoto K, Ueno T, Okamoto K, Fujimura S (1980) Experimental model for combination chemotherapy with metronidazol using human uterine cervical carcinomas transplanted into nude mice. Cancer Res 40:4287–4294PubMedGoogle Scholar
  25. 25.
    Tsuji T, Okada F, Yamaguchi O, Nakamura T (1990) Molecular cloning of the large subunit of transforming growth factor type b masking protein and expression of the mRNA in various rat tissues. Proc Natl Acad Sci USA 87:8835–8839PubMedGoogle Scholar
  26. 26.
    Udagawa Y, Nozawa S, Tsukazaki K, Ohta H, Akiba T, Kurihara S (1984) Biological properties of two newly established cell lines (SKG-IIIa, IIb) from a human uterine cervical epidermoid carcinoma. Acta Obst Gynaec Jpn 36:237–246 [in Japanese]Google Scholar
  27. 27.
    Watson JM, Sensintaffar JL, Berek JS, Martinex-Maza O (1990) Constitutive production of interleukin 6 by ovarian cancer cell lines and by primary ovarian tumor cultures. Cancer Res 50:6959–6965PubMedGoogle Scholar
  28. 28.
    Watson JM, Berek JS, Martinez-Maza O (1993) Growth inhibition of ovarian cancer cells induced by antisense IL-6 oligonucleotides. Gyenecol Oncol 49:8–15Google Scholar
  29. 29.
    Woodworth DC, Simpson S (1993) Comparative lyphokine secretion by cultured normal human cervical keratinocytes, papilloma virus-immortalized, and carcinoma cell lines. Am J Pathol 142:1544–1555PubMedGoogle Scholar
  30. 30.
    Yamada T, Ueda M, Maeda T, Miyawaki Y, Misaki O, Ueki M, Sugimoto O (1987) Establishment and characterization of a cell line (OMC-4) originating from a human adenocarcinoma of the uterine cervix. Acta Obst Gynaec Jpn 39:859–860Google Scholar
  31. 31.
    Yamasaki K, Taga T, Hirata Y, Yawata H, Kawanishi Y, Seed B, Taniguchi T, Hirano T, Kishimoto T (1988) Cloning and expression of the human interleukin-6 (BSF-2/INFβ2) receptor. Science 241:825–828PubMedGoogle Scholar
  32. 32.
    Yoshikawa H, Kawana T, Kitagawa K, Mizuno M, Yoshikura H, Iwamoto A (1991) Detection and typing of multiple genital human papilloma viruses by DNA amplification with consensus primers. Jpn J Cancer Res 82:524–531PubMedGoogle Scholar
  33. 33.
    Yoshizaki K, Nishimoto N, Matsumoto K, Tagoh H, Taga T, Deguchi Y, Kuritani T, Hirano T, Hashimoto K, Okada N, Kishimoto T (1990) Interleukin-6 and expression of its receptor on epidermal keratinocytes. Cytokines 2:381–387Google Scholar

Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • H. Takanol
    • 1
  • K. Harigaya
    • 1
  • G. Ishii
    • 2
  • Y. Sugaya
    • 2
  • S. Soeta
    • 2
  • T. Nunoyamal
    • 1
  • H. Shirasawa
    • 3
  • K. Shimizu
    • 3
  • H. Tokita
    • 4
  • B. Simizu
    • 3
  • A. Mikata
    • 2
  • S. Sekiya
    • 1
  1. 1.Department of Obstetrics and GynecologyChiba University School of medicineChibaJapan
  2. 2.Department of 1st PathologyChiba University School of medicineChibaJapan
  3. 3.Department of 1st MicrobiologyChiba University School of medicineChibaJapan
  4. 4.Division of Animal ResearchChiba Cancer Center Research InstituteChibaJapan

Personalised recommendations