Elsevier

Gynecologic Oncology

Volume 83, Issue 2, November 2001, Pages 235-243
Gynecologic Oncology

Regular Article
Cytokine Profile of Cervical Cancer Cells

https://doi.org/10.1006/gyno.2001.6378Get rights and content

Abstract

Objective. In patients with cervical carcinoma, the presence of cytokines produced by TH2 cells, and the presence of an eosinophilic inflammatory infiltrate, has been associated with a less effective immune response and tumor progression. In the present study, we have investigated the cytokine profile of cervical carcinoma cells. In addition, we have measured whether differences in cytokine profiles between normal and malignant cervical epithelial cells are present.

Methods. For this purpose we have determined the mRNA expression patterns of 20 relevant cytokines by RT-PCR and Southern blotting in 3 normal primary cervical epithelial cell cultures (NPE) and 10 cervical cancer cell lines (CCCL).

Results. TGF-β1, IL-4, IL-12p35, and IL-15 were produced by all CCCL and NPE. TNF-α, IL-10, IL-5, and RANTES were present in most NPE, but not in any of the CCCL. MCP-1 was expressed in all CCCL but in only one NPE. The presence of the anti-inflammatory cytokine TGF-β1 in cervical carcinomas was confirmed by RNA in situ hybridization on tissue sections of carcinomas from which the CCCL originated.

Conclusions. Our results suggest that cervical carcinoma cells produce immunomodulatory cytokines and that cytokine expression patterns change after malignant transformation. The implications of locally produced cytokines by cervical cancer cells are further discussed.

References (53)

  • IARC Working Group. IARC monographs on the evaluation of carcinogenic risk to humans. London: Oxford Univ. Press,...
  • H Zur Hausen

    Papillomavirus infections—a major cause of human cancers

    Biochim Biophys Acta

    (1996)
  • C Benton et al.

    Human papillomavirus in the immunosuppressed

    Papillomavirus Rep

    (1992)
  • K Petry et al.

    Cellular immunodeficiency enhances the progression of human papillomavirus-associated cervical lesions

    Int J Cancer

    (1994)
  • AA Ozsaran et al.

    Evaluation of the risk of cervical intraepithelial neoplasia and human papilloma virus infection in renal transplant patients receiving immunosuppressive therapy

    Eur J Gynaecol Oncol

    (1999)
  • H Nakagomi et al.

    Lack of interleukin-2 (IL-2) expression and selective expression of IL-10 mRNA in human renal cell carcinoma

    Int J Cancer

    (1995)
  • M Huang et al.

    Human non-small cell lung cancer cells express a type 2 cytokine pattern

    Cancer Res

    (1995)
  • E Tartour et al.

    Prognostic value of intratumoral interferon gamma messenger RNA expression in invasive cervical carcinomas

    J Natl Cancer Inst

    (1998)
  • K Kleine-Lowinski et al.

    Monocyte-chemo-attractant-protein-1 (MCP-1)-gene expression in cervical intra-epithelial neoplasias and cervical carcinomas

    Int J Cancer

    (1999)
  • CD Woodworth et al.

    Comparative lymphokine secretion by cultured normal human cervical keratinocytes, papillomavirus-immortalized, and carcinoma cell lines

    Am J Pathol

    (1993)
  • F Linnell et al.

    The prognostic value of eosinophilic leukocytes in the stroma of carcinoma of the cervix uteri: a study of 291 cases treated with radium and roentgen therapy

    Acta Radiol

    (1954)
  • JT Lasersohn et al.

    Carcinoma of the uterine cervix

    Cancer

    (1964)
  • SG Bostrom et al.

    Carcinomas of the cervix with intense stromal eosinophilia

    Cancer

    (1981)
  • KE De Visser et al.

    Effects of TGF-β on the immune system: implications for cancer immunotherapy

    Leukemia

    (1999)
  • M Clerici et al.

    Cytokine production patterns in cervical intraepithelial neoplasia: association with human papillomavirus infection

    J Natl Cancer Inst

    (1997)
  • WJ van Driel et al.

    The current status of therapeutic HPV vaccine

    Ann Med

    (1996)
  • Cited by (71)

    • Cytokine expression profiles in cervical mucus from patients with cervical cancer and its precursor lesions

      2019, Cytokine
      Citation Excerpt :

      Cytokines are secreted by dendritic cells, macrophages, epithelia, and fibroblasts [22], and identifying the components of cervical neoplasia (such as hematopoietic cells, epithelia, or surrounding stromal cells) responsible for secreting specific cytokines is difficult. Proinflammatory or inhibitory cytokines are secreted from cervical neoplastic cells [12,23–26], and chemokines, such as MCP-1 and RANTES, are secreted from monocytes, macrophages, fibroblasts, T cells [22], and cancer cells [10,27,28]. The production of these cytokines by tumors results from complex interactions between tumor and non-tumor cells, with both cell types contributing to cytokine production [27].

    View all citing articles on Scopus
    View full text