Expression of integrins and Toll-like receptors in cervical cancer: effect of infectious agents

Innate Immun. 2012 Feb;18(1):55-69. doi: 10.1177/1753425910392934. Epub 2011 Jan 14.

Abstract

We hypothesized that development of cervical cancer is associated with alterations in the expression of innate immune receptors, i.e. integrins and TLRs, and that these alterations can be induced by infectious agents. We have studied the expression of these proteins in cervical biopsy tissues and cervical cancer-derived cell lines HeLa, CaSki, SiHa, C-33 A, and ME180. Immunohistochemistry analysis demonstrated an increase in integrin αv, β3, β4, and β6 expression in the epithelium during the development of cervical cancer. A clear trend towards higher expression of integrin β6 in cell lines harbouring human papillomavirus (HPV) genetic material, compared to HPV-negative C-33 A, was observed. To investigate whether bacterial infection can alter the expression of TLRs and integrins, we infected HeLa cells by two pathogens, Escherichia coli and Pseudomonas aeruginosa, using a common bacterium of the female genital tract, Lactobacillus reuteri, as a control. Infection with E. coli or P. aeruginosa, but not with L. reuteri, significantly altered the expression of TLR and integrins, particularly of TLR4 and integrin β6. Considering that both integrin β6 and TLR4 play important roles in tumorigenesis, our data suggest that bacterial infection may trigger cancer development in HPV-infected cervical epithelium.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alphapapillomavirus / immunology*
  • Alphapapillomavirus / pathogenicity
  • Bacterial Infections / complications
  • Bacterial Infections / immunology*
  • Bacterial Infections / pathology
  • Carcinoma / complications
  • Carcinoma / immunology*
  • Carcinoma / pathology
  • Cell Transformation, Neoplastic / immunology
  • Cervix Uteri / pathology*
  • Epithelial Cells / immunology
  • Epithelial Cells / metabolism*
  • Epithelial Cells / microbiology
  • Epithelial Cells / pathology
  • Epithelial Cells / virology
  • Female
  • Gene Expression Regulation / immunology
  • HeLa Cells
  • Humans
  • Immunohistochemistry
  • Integrin beta Chains / genetics
  • Integrin beta Chains / immunology
  • Integrin beta Chains / metabolism
  • Papillomavirus Infections / complications
  • Papillomavirus Infections / immunology*
  • Papillomavirus Infections / pathology
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / immunology
  • Toll-Like Receptor 4 / metabolism
  • Uterine Cervical Neoplasms / complications
  • Uterine Cervical Neoplasms / immunology*
  • Uterine Cervical Neoplasms / pathology

Substances

  • Integrin beta Chains
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • integrin beta6